Quality by design compliant strategy for the development of a liquid chromatography–tandem mass spectrometry method for the determination of selected polyphenols in Diospyros kaki J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-18 C. Ancillotti, S. Orlandini, L. Ciofi, B. Pasquini, C. Caprini, C. Droandi, S. Furlanetto, M. Del Bubba
Diospyros kaki fruits possess great beneficial properties for human health due to their strong antioxidant and antiradical activities related to the high level of bioactive compounds and particularly polyphenols. In this paper a rapid and efficient liquid chromatography–tandem mass spectrometry method for the determination of 38 polyphenolic compounds in Diospyros kaki flesh was developed. The optimization of the chromatographic method was performed applying a Quality by Design approach, which is unexplored in the field of food analysis. The Critical Method Attributes (CMAs) were the critical resolutions of some isobaric compounds and analysis time. The Critical Methods Parameters (CMPs) were related to the characteristics of both the mobile phase and the column: flow rate, temperature, starting organic phase concentration of the mobile phase, formic acid percentage in the eluents, type of organic solvent in the mobile phase and gradient of organic eluents. The effects of the CMPs on the CMAs were evaluated by experimental design, at first carrying out a screening phase by an asymmetric screening matrix and then applying Response Surface Methodology by a Doehlert Design. The quadratic polynomial models postulated to link the CMAs to CMPs were calculated and the Method Operable Design Region was identified with the aid of Monte Carlo simulations as the multidimensional combination of the CMPs that satisfied the requirements for the CMAs with a probability ≥90%. The developed method was applied to real samples obtained by the extraction of Diospyros kaki flesh from two different cultivars (Rojo Brillante and Kaki Tipo), making it possible to obtain extensive information on their polyphenolic profiles.
Thermodynamics of the adsorption of monoclonal antibodies in phenylboronate chromatography: affinity versus multimodal interactions J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Sara A.S.L. Rosa, C.L. da Silva, M. Raquel Aires-Barros, A.C. Dias-Cabral, Ana M. Azevedo
The aim of this work was to investigate the complex phenomena underlying the adsorption of an anti-human IL-8 (anti-IL8) monoclonal antibody (mAb) to m-aminophenylboronate (m-APBA) by Flow Microcalorimetry (FMC) and to understand the role of non-specific interactions in the adsorption process. FMC was exploited as a dynamic on-line method to measure instantaneous heat energy transfers in order to understand the surface phenomena underlying mAb’s adsorption towards the synthetic ligand m-APBA under different pH (7.5, 8.5, 9.0, 9.5 and 10.0) and salt concentrations (0 and 150 mM NaCl). Results showed that the adsorption of anti-IL8 mAb to m-APBA is enthalpically driven (ΔHads<0), as expected for the predominant reversible esterification reaction between boronates and cis-diols-containing molecules. For all the pH conditions studied, thermograms presented a first exothermic peak, characteristic of the reversible esterification reaction between mAb (pI≥9.3) and m-APBA (pKa = 8.8), except at pH 9.0 in the presence of 150 mM NaCl, for which the thermogram presented a first endothermic peak. The heat of adsorption (ΔHads) obtained at conditions where cis-diol interactions were predominant was approximately −243 ± 38 kJ/mol against −82 ± 14 kJ/mol (p-value < 0.05) obtained at pH 9.0 with 150 mM NaCl. The observed shift in the thermogram profile at pH 9.0, 150 mM NaCl, and the consequent decrease of 60–70% in ΔHads were indicative of the promotion of electrostatic interactions between the protein and the ligand. Overall, and whereas the binding of the PBA ligand to mAb molecules has been described for decades as being affinity-based, our study demonstrates the multimodal behaviour of this interaction and contributes towards the understanding of the adsorption thermodynamics.
Investigating the Impact of Aromatic Ring Substitutions on Selectivity for a Multimodal Anion Exchange Prototype Library J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Julie Robinson, Mark A. Snyder, Chris Belisle, Jia-li Liao, Hong Chen, Xuemei He, Yueping Xu, Steven M. Cramer
The increasing prevalence of low pI non-mAb therapeutics as well as current challenges in mAb-aggregate separations and low recoveries motivate further development in the multimodal anion exchange (MM AEX) space. In this work, linear salt gradient experiments at pH 7 were used to evaluate the retention of model proteins (with pI from 3.4 to 6.8) in 17 novel MM AEX prototype systems. The ligands were organized into three series. Series 1 extended previous work in multimodal ligand design and included a hydroxyl variant and linker length variants. Series 2 and 3 investigated the nature of hydrophobicity in MM AEX systems by adding hydrophobic (series 2) or fluorine (series 3) substituents to a solvent exposed phenyl ring. Compared to the commercial resin Capto Adhere, the series 1 and 3 ligands exhibited weaker binding, while some of the series 2 aliphatic prototypes showed dramatically increased retention and unique selectivities. Within series 1, the model proteins eluted earlier in the gradient as the charge-hydrophobic group distance on the ligand was increased from 4.9 Å to 8.5 Å. For the aliphatic variants in series 2, proteins that eluted early in the salt gradient were not affected by the increase in ligand hydrophobicity, while the later eluting proteins bound stronger as the length of the aliphatic substituent increased. The series 3 variants indicated that phenyl ring fluorination created subtle changes in protein elution in these MM AEX systems. Retention data from the three series was used to generate a partial least squares QSAR model based on both protein and ligand descriptors which accurately predicted protein retention with a training R2 of 0.81 and a test R2 of 0.76. The retention characteristics of some prototypes such as the earlier elution and unique selectivities compared to Capto Adhere suggest that they could potentially provide unique selectivities and increased recovery for the downstream processing of both mAb and non-mAb biotherapeutics.
Study of the temperature effect on the acid-base properties of cellulose acrylate by inverse gas chromatography at infinite dilution J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Tayssir Hamieh
Inverse gas chromatography (IGC) at infinite dilution was used to characterize the surface and interfacial properties of polymers, oxides or polymers adsorbed on oxides. In this paper, the dispersive component of the surface energy of CA was calculated following the molecular models of the surface areas of n-alkanes proving the presence of two linear zones with two different slopes in the temperature intervals and indicating a change in the structure of CA groups. The acid-base properties in the Lewis terms of cellulose acrylate were determined. One proved that the specific enthalpy and entropy of interaction of polar probes are functions of the temperature The application of Hamieh’s model allows to the determination of the acid-base constants KA and KD and the amphoteric constant K of cellulose acrylate surface. It was proved that the constants KA, KD and K of cellulose acrylate strongly depend on the temperature. This study allowed us to determine the probability w of the specific adsorption of polar probes on the cellulose acrylate surface. This probability parameter also depends on the temperature.
Simultaneous determination of trace Aflatoxin B1 and Ochratoxin A by aptamer-based microchip capillary electrophoresis in food samples J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Meng-Wei Xiao, Xiao-Lin Bai, Yi-Ming Liu, Li Yang, Xun Liao
An aptamer-based microchip capillary electrophoresis coupled with laser induced fluorescence (MCE-LIF) detection method for fast determination of Aflatoxin B1(AFB1) and Ochratoxin A (OTA) was developed. Aptamers that are specific to these two mycotoxins were first hybridized with their aptamer complementary oligonucleotides. The double strand DNA that comes in contact with mycotoxin-containing environment would be unwound into separate aptamer-mycotoxin complex and aptamer complementary single strand. Different types of oligonucleotides can be separated in MCE and detected under the aid of fluorescent dye SYBR gold in LIF detection unit. Under the optimal conditions, on-chip aptamer-mycotoxin conjugates analysis was achieved within 3 min with extremely low LODs (0.026 ng/mL for AFB1 and 0.021 ng/mL for OTA). Specificity study indicated that other major mycotoxins would not cross-react with these two aptamers, demonstrating the good selectivity of the proposed method. Quantification of trace AFB1 and OTA in real food samples was carried out and satisfactory recoveries were obtained. It is demonstrated that this method is fast, facile and specific for Simultaneous determination of trace AFB1 and OTA from foodstuffs.
Simultaneous analysis of spectinomycin, halquinol, zilpaterol, and melamine in feedingstuffs by ion-pair liquid chromatography-tandem mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Luciano Molognoni, Naielly Coelho de Souza, Leandro Antunes de Sá Ploêncio, Gustavo Amadeu Micke, Heitor Daguer
A method for the simultaneous analysis of veterinary drug residues (spectinomycin, halquinol, and zilpaterol) and contaminants (melamine) in feedingstuffs by liquid chromatography-tandem mass spectrometry was developed. Method performance for all analytes was evaluated by reversed-phase liquid chromatography, reversed-phase with altered chemical equilibrium, and hydrophilic interaction (HILIC) as chromatographic modes. Validation was in accordance to Commission Decision 657/2002/CE, by considering the best chromatographic approach. Ion-pair liquid chromatography with C18 as stationary phase led to the lowest random uncertainties, effective analyte separation and shorter time of analysis. Low precision deviations and good recovery rates were obtained and thus method reliability and sensitivity could be consolidated. Method applicability was evaluated by the analysis of samples of feedingstuffs, such as cattle, pig, and poultry feeds, feed ingredients of both animal and vegetable origins, and mineral feeds. Some samples showed quantifiable concentrations of halquinol and zilpaterol, reinforcing the importance of this new analytical control method.
Dynamically modified C18 silica monolithic column for the rapid determinations of lead, cadmium and mercury ions by reversed-phase high-performance liquid chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 M. Thirumalai, S. Naveen Kumar, D. Prabhakaran, N. Sivaraman, M. Akhila Maheswari
In this article, a new reversed-phase high-performance liquid chromatography (RP-HPLC) method for the rapid, selective and sequential separation of toxic heavy metal ions namely, Pb2+, Hg2+, and Cd2+ is reported. For this RP-HPLC method, a C18 silica monolith column (Chromolith RP-18e, 100 × 4.6 mm) has been surface modified using a laboratory-synthesized amphiphilic organic ligand namely, 1,5-dioctanoyl-1,5-diphenylcarbazide (DODPC), which acts an ion-selective receptor, for the separation of the target analytes. The eluted metal ions were subjected to post-column derivatization reaction with 4-(2-pyridylazo) resorcinol (PAR) prior to their detection using a UV–vis detector (at 520 nm). The post-column reagent (PAR; 4.7 × 10−4 M; pH 9.0; 1.5 mL/min) was mixed with the column eluate through an ingeniously designed T-connector. An ultra-fast separation of Pb2+, Cd2+, and Hg2+ ions with a retention time of 1.67, 1.88 and 3.62 min, respectively was achieved, using 0.0526 mmol of DODPC coated C18 monolithic column along with tartaric acid solution (1.0 × 10−2 M; pH 4.0; 1.0 mL/min), as the isocratic eluent (mobile phase). The chromatographic parameters such as linearity, accuracy, recovery, limits of detection and quantification were validated to achieve superior analytical results. The influence of various analytical parameters such as nature of mobile phase and its concentration, solution pH, flow rate, post-column reagent and its concentration were studied and optimized. The studies revealed a lower detection limits of 0.075, 0.090 and 0.120 μg/L, and a quantification limits of 0.225, 0.270 and 0.450 μg/L, for Pb2+, Cd2+ and Hg2+ ions, respectively. A linear signal response in the concentration range of 0.05–50.0 μg/mL, was observed for the target metal ions, with an average r2 value of 0.9994. The method was selective for the target metal ions, with excellent data reliability and reproducibility that accounts for an average recovery value of 99.76%, with a relative standard deviation of ≤1.83%.
Poly(3-hexylthiophene) stationary phase for gas chromatographic separations of aliphatic and aromatic isomers J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Jianlin Peng, Meiling Qi
This work describes the investigation of utilizing a chain-typed thiophene-based π-conjugated polymer, i.e., poly(3-hexylthiophene) (P3HT), as the stationary phase for gas chromatography (GC). The P3HT column was statically prepared and investigated for its column efficiency, polarity, separation performance, repeatability and thermal stability. As a result, it showed moderate polarity and column efficiencies of 3260, 3310 and 3790 plates/m for 1-octanol, naphthalene and n-dodecane, respectively. As evidenced, it exhibited high-resolution performance for aliphatic and aromatic isomers, including those critical pairs such as phenanthrene/anthracene and p-/m-benzenediol isomers. Moreover, it displayed stronger retention for alkanes, alcohols and phenols in comparison to the polysiloxane stationary phase with close polarity. Also, the P3HT column had good repeatability and reproducibility with the RSD values less than 0.05% for run-to-run, 0.17-0.54% for day-to-day and 2.7-5.2% for column-to-column, and good thermal stability up to 260 °C. This work demonstrates the promising future of the thiophene-based polymer and its derivatives in separation science.
Contemporary theory of enantioseparations in capillary electrophoresis J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Bezhan Chankvetadze
The first separation of enantiomers in capillary electrophoresis (CE) counts slightly longer than three decades. Fast development of the practice and theory of chiral CE occurred in the past 30 years and today one can consider this technology to have a solid and mature theoretical background. The goal of the present review is not only to summarize the history and contemporary theory of enantioseparations by using CE but also to present the authors personal view where shall we head to with this attractive technology not only from the viewpoint of separation of enantiomers but also for better understanding the mechanisms of non-covalent (enantioselective) interactions in chemistry, biology, medicine and related disciplines.
An effective strategy for controlled fabrication and self-assembled modification of template-supported silica nanosheets on a superelastic nickel-titanium alloy fiber for highly efficient solid-phase microextraction J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-17 Shanshan Zhou, Huiju Wang, Panxia Jin, Ziyi Wang, Xuemei Wang, Xinzhen Du
Silica nanosheets (SiO2NSs) were successfully fabricated on the superelastic nickel-titanium alloy (NiTi) wire as a novel fiber for solid-phase microextraction (SPME). Before sol-gel coating, the NiTi wire was hydrothermally treated in alkaline solution for the in situ growth of NiO/TiO2 nanosheets (NiO/TiO2NSs). The sol-gel coating of SiO2 on the surface of NiO/TiO2NSs template was investigated and a thin shell of SiO2 was found to cover NiO/TiO2NSs, which can enlarge the effective surface area of the SiO2 coating. This SiO2 capped NiO/TiO2NSs coated NiTi (NiTi@NiO/TiO2@SiO2NSs) fiber shows good extraction selectivity for polycyclic aromatic hydrocarbons (PAHs) and enhanced mechanical stability. After the self-assembled modification of SiO2NSs by phenyltrichlorosilane, the NiTi@NiO/TiO2@SiO2NSs@Ph fiber shows higher extraction capability for non-polar PAHs. Thus, the conditions for the extraction of PAHs were investigated and optimized coupled to HPLC with UV detection. Under the optimized conditions, the analytical parameters of the SPME-HPLC methods with the NiTi@NiO/TiO2@SiO2NSs and the NiTi@NiO/TiO2@SiO2NSs@Ph fibers were determined and compared. The SPME-HPLC method with the NiTi@NiO/TiO2@SiO2NSs@Ph fiber was developed for the concentration and the determination of PAHs in environment water samples. The relative recovery of PAHs in real water samples spiked at 5 μg L-1, 10 μg L-1 and 30 μg L-1 ranged from 88.1% to 109%. Furthermore, this fiber is stable due to the chemical bonding between different coatings and NiTi substrates. The fabrication of the NiO/TiO2@SiO2NSs@Ph coating on the NiTi fiber substrate is precisely controllable.
Investigation of robustness for supercritical fluid chromatography separation of peptides: Isocratic vs gradient mode J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-10 Martin Enmark, Emelie Glenne, Marek Leśko, Annika Langborg Weinmann, Tomas Leek, Krzysztof Kaczmarski, Magnus Klarqvist, Jörgen Samuelsson, Torgny Fornstedt
We investigated and compared the robustness of supercritical fluid chromatography (SFC) separations of the peptide gramicidin, using either isocratic or gradient elution. This was done using design of experiments in a design space of co-solvent fraction, water mass fraction in co-solvent, pressure, and temperature. The density of the eluent (CO2-MeOH-H2O) was experimentally determined using a Coriolis mass flow meter to calculate the volumetric flow rate required by the design. For both retention models, the most important factor was the total co-solvent fraction and water mass fraction in co-solvent. Comparing the elution modes, we found that gradient elution was more than three times more robust than isocratic elution. We also observed a relationship between the sensitivity to changes and the gradient steepness and used this to draw general conclusions beyond the studied experimental system. To test the robustness in a practical context, both the isocratic and gradient separations were transferred to another laboratory. The gradient elution was highly reproducible between laboratories, whereas the isocratic system was not. Using measurements of the actual operational conditions (not the set system conditions), the isocratic deviation was quantitatively explained using the retention model. The findings indicate the benefits of using gradient elution in SFC as well as the importance of measuring the actual operational conditions to be able to explain observed differences between laboratories when conducting method transfer.
Green techniques in comparison to conventional ones in the extraction of Amaryllidaceae alkaloids: Best solvents selection and parameters optimization J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-11 Sarah S. Takla, Eman Shawky, Hala M. Hammoda, Fikria A. Darwish
An undisputed trend in sample preparation at present is to meet the requirements of green chemistry especially in the field of natural products. Green technology continuously pursues new solvents to replace common organic solvents that possess inherent toxicity. Over the past two decades, non-ionic surfactants have gained enormous attention from the scientific community. The micelle-mediated extraction and cloud-point preconcentration (CPE) methods offer a convenient alternative to the conventional extraction systems. Recently, natural deep eutectic solvents (NDESs) have emerged as green and sustainable solvents for efficient extraction of bioactive compounds or drugs. They are generally composed of neutral, acidic or basic compounds that form liquids of high viscosity when mixed in certain molar ratio. The presented work aimed to comprehensively compare and evaluate the potential and effectiveness of NDES as well as non-ionic surfactants (Genapol X-080, Triton X-100 and Triton X-114) for extraction of Amaryllidaceae alkaloids from Crinum powellii bulbs as representative example of plant material, in comparison to the conventional solvents (methanol, ethanol and water).A new validated high-performance thin-layer chromatographic (HPTLC) method has been developed for the simultaneous quantitation of three alkaloids markers, lycorine, crinine and crinamine, in the bulbs of C. powellii. Extraction efficiency of the targeted alkaloids from the bulb matrix with organic and ecofriendly (green) solvents were studied. Results revealed that NDES and surfactants were significantly more efficient in alkaloid extraction than previous methods requiring the consumption of organic solvents and water. Genapol X-80 demonstrated 138%, 149 % and 145%, while choline chloride: fructose (5:2): H2O (35%) NDES mixture demonstrated 243%, 225 % and 238% of the total alkaloidal extraction capacity of ethanol, methanol and water, respectively at 50 °C for extraction time 1 hour using ultrasonication for all experiments. Furthermore, Box–Behnken response surface design combined with the overall desirability value were successfully employed to optimize and study the individual and interactive effect of process variables such as extraction temperature, time and surfactant %, for Genapol X-80, and sonication extraction temperature, time and water concentration, for choline chloride: fructose: H2O NDES mixture, on the alkaloidal yield from C. powellii. It was evident that parameters interacting together can act in synergism if adjusted properly according to the optimized conditions to obtain maximum alkaloids extractability. It is for the first time that the efficiency of micelle-mediated extraction has been compared to that of natural deep eutectic solvents for the extraction of alkaloids and the results thoroughly discussed.
Enantiomeric ratios: why so many notations? J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-11 Maria E Tiritan, Carla Fernandes, Alexandra S. Maia, Madalena Pinto, Quezia B. Cass
The correct quantification of enantiomers is pivotal in a variety of fields, such as pharmacokinetic studies, enantioselective syntheses, chemical characterization of natural products, authentication of fragrance and food, biodegradation behavior, accurate evaluation of environmental risk, and it can also provide information for sentencing guidance in forensic field. Enantioselective chromatography is the first choice to assess the composition of an enantiomeric mixture. Different notations have been used to express the measured enantiomeric ratios, which compromise the results and represent a challenge for data comparison. This manuscript critically discusses the currently used notations and exemplifies with applications in different fields indicating the advantages and disadvantages of one of the adopted systems. In order to simplify the notations, the use of enantiomeric ratio (e.r.%) as standardization for nonchiroptical methods is proposed.
Numerical correction for asymmetrical peak profiles for moment analysis of chromatographic behavior J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-09 Kanji Miyabe
A numerical correction method is proposed for the moment analysis of some properties of chromatographic columns, even when the profiles of their elution peaks exhibit some asymmetry. Information on the retention equilibrium and the mass transfer kinetics of a C18-silica gel packing material is derived by the moment analysis from the experimental data obtained under three different sets of conditions: (1) the tailing peaks eluted from the column used; they are not corrected by the numerical method; (2) the same peaks are corrected by the numerical method, which provides the information on the column radial heterogeneity and on the efficiency at its center; and (3) symmetrical peaks having nearly Gaussian profiles eluted from another column packed with the same material; these peaks are not corrected by the numerical method. The analytical results obtained under the three different conditions are compared. The results demonstrate that the numerical correction method allows the determination of the information on the chromatographic behavior of columns from asymmetrical peak profiles, i.e., column efficiency at radial center, order of the polynomial functions for representing the radial distributions of mobile phase flow velocity and column efficiency, ratio of the flow velocity near the wall to that at the column center, and ratio of the column efficiency near the wall to that at the column center.
Protein purification using solid-phase extraction on temperature-responsive hydrogel-modified silica beads J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-09 Kohei Okubo, Koji Ikeda, Ayaka Oaku, Yuki Hiruta, Kenichi Nagase, Hideko Kanazawa
Recently, the importance of biopharmaceuticals in medical treatments has been increasing, and effective protein purification methods are strongly required for their production. In the present study, a temperature-responsive solid-phase extraction (SPE) column was developed for the purification of proteins without affecting their bioactivity. A temperature-responsive polymer hydrogel-modified stationary phase was prepared by coating aminopropyl silica beads (average diameter, 40–64 μm) with poly(N-isopropylacrylamide) (PNIPAAm)-based thermoresponsive hydrogels. n-Butyl methacrylate and acrylic acid were copolymerized with PNIPAAm as hydrophobic and anionic monomers, respectively. Using these temperature-responsive SPE columns, targeted proteins were retained on the thermoresponsive hydrogel at 40 °C through hydrophobic and electrostatic interactions. After the temperature was reduced from 40 °C to 4 °C, the retained proteins were successfully eluted from the column. Using the temperature-responsive SPE system, lysozyme was successfully separated from ovalbumin without any loss in bioactivity (99.7 ± 0.1%). Rituximab, a monoclonal antibody, was also purified from BSA or hybridoma cell culture medium using the prepared SPE column. Denaturation of rituximab was not observed in the rituximab fraction eluted from the SPE column. These results demonstrate that temperature-responsive polymer-based SPE can be applied in biomedical purifications, while maintaining the biological activity of the proteins.
Fabricated ultrathin magnetic nitrogen doped graphene tube as efficient and recyclable adsorbent for highly sensitive simultaneous determination of three tetracyclines residues in milk samples J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Qiong Wang, Lei Zhang
In this work, ultrathin magnetic nitrogen doped graphene tube (mNi@N-GrT) is synthetized via a template free graphitization process. The mNi@N-GrT as magnetic solid phase extraction adsorbent is used to extract three tetracyclines (TCs), showing the best extraction ability and adsorption capacity than graphene, MWCNT and magnetic MWCNT (NiFe2O4/MWCNT). The tubular structure of mNi@N-GrT can avoid the aggregation problem, provide higher active surface area and larger conjugated system. The doping of N atom will generate structural defects which will be adsorption sites for three TCs. Furthermore, the mNi@N-GrT with magnetic properties is beneficial to the recovery and recycle. The limits of detections (LODs) (S/N = 3:1) are in the range of 1.29–2.31 ng mL−1 with average recoveries from 91.6 to 109.7% in milk samples. The results demonstrate that the mNi@N-GrT is a hopeful adsorbent in the MSPE of TCs in real samples.
Lipidomic alterations in lipoproteins of patients with mild cognitive impairment and Alzheimer’s disease by asymmetrical flow field-flow fractionation and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 San Ha Kim, Joon Seon Yang, Jong Cheol Lee, Ji-Yeon Lee, Jun-Young Lee, Eosu Kim, Myeong Hee Moon
Alzheimer’s disease (AD) is an irreversible neurodegenerative disorder with the clinical symptom of the progressive loss of cognitive function and mild cognitive impairment (MCI) is a translational state between cognitive changes of normal aging and AD. Lipid metabolism and pathogenesis of Alzheimer’s disease (AD) are closely linked. Despite obviously discrete lipidome constitutions across lipoproteins, lipidomic approaches of AD has been mostly conducted without considering lipoprotein-dependent alterations. This study introduces a combination of asymmetrical flow field-flow fractionation (AF4) and nanoflow ultrahigh performance liquid chromatography-tandem mass spectrometry (nUHPLC-ESI-MS/MS) for a comprehensive lipid profiling in different lipoprotein level of patients plasma with AD and amnestic MCI in comparison to age-matched healthy controls. Lipoproteins in plasma samples were size-sorted by a semi-preparative scale AF4, followed by non-targeted lipid identification and high speed targeted quantitation with nUHPLC-ESI-MS/MS. It shows 14 significantly altered high abundance lipids in AD, exhibiting >2-fold increases (p < 0.01) in LDL/VLDL including triacylglycerol, ceramide, phosphatidylethanolamine, and diacylglycerol. Three lipid species (triacylglycerol 50:1, diacylglycerol 18:1_18:1, and phosphatidylethanolamine 36:2) showing a strong correlation with the degree of brain atrophy were found as candidate species which can be utilized to differentiate the early stage of MCI when simple Mini-Mental State Examination results were statistically incorporated. The present study elucidated lipoprotein-dependent alterations of lipids in progression of MCI and further to AD which can be utilized for the future development of lipid biomarkers to enhance the predictability of disease progress.
Quantification of alcohols, diols and glycerol in fermentation with an instantaneous derivatization using trichloroacetyl isocyanante via liquid chromatography-massspectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Jun Chen, Dayu Chen, Xiaofan Zhang, Meng Wang, Biqiang Chen, Dongge An, Li Xu, Qiang Lyu
A sensitive LC–MS/MS method was established to quantify diols and glycerol in fermentation broth using trichloroacetyl isocyanate as instantaneous derivatization reagent for monitoring the production of 1,3-propanediol and 2,3-butanediol from the biodiesel biorefinery process. Due to the derivatization reaction was very quickly at room temperature, only 1 min was needed for the reaction process. In addition, both extraction of analytes and evaporation of water were not employed in the analytical procedure. Furthermore, the isotope of chlorine was beneficial for understanding of the secondary mass spectrum and avoiding false positive results. Therefore, much more accurate results of diols and glycerol concentration in fermentation could be obtained even at very low levels for the evaluation of microbial metabolism pathway modification.
Using single-isomer octa(6-O-sulfo)-γ-cyclodextrin for fast capillary zone electrophoretic enantioseparation of pindolol: Determination of complexation constants, software-assisted optimization, and method validation J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Lívia Kanizsová, Martin Ansorge, Iva Zusková, Pavel Dubský
The present study describes a rapid and effective capillary electrophoresis (CE) method for the enantioseparation of pindolol using single-isomer octa(6-O-sulfo)-γ-cyclodextrin. The complexation parameters were determined under neutral and high pH conditions to identify optimal separation conditions using a theoretical model. Baseline separation of pindolol enantiomers was achieved within 6 min in a sodium/MOPS buffer, pH 7.2, with a selector concentration of 6 mM. The method was validated according to the ICH guidelines using imidazole as an internal standard. Low limits of detection and quantification were found, specifically 1.2 μg/mL and 4 μg/mL (0.6 μg/mL and 2 μg/mL per enantiomer), respectively. The calibration curves showed good linearity, with a coefficient of determination R2 ≥ 0.999 over a 5 – 55 μg/mL concentration range and over a 50 – 300 μg/mL concentration range of the racemic mixture. The relative standard deviations (%RSD) of intra-day and inter-day precision were lower than 8% at LOQ level, lower than 3% at 50 μg/mL level and lower than 1.5% at 300 μg/mL level. Accuracy ranged from 95 to 103% (106% at LOQ level). The proposed method was successfully tested on a medical formulation of Visken® Sandoz intravenous solution and Visken® Teofarma pills for oral use.
Chiral capillary zone electrophoresis in enantioseparation and analysis of cinacalcet impurities: use of Quality by Design principles in method development J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Benedetta Pasquini, Serena Orlandini, Mercedes Villar-Navarro, Claudia Caprini, Massimo Del Bubba, Michal Douša, Alessandro Giuffrida, Roberto Gotti, Sandra Furlanetto
A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π≥90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5 cm; temperature, 18 °C; voltage, 26 kV (26-27 kV); background electrolyte, 150 mM phosphate buffer pH 2.70 (2.60-2.80), 3.1 mM (3.0-3.5 mM) HPγCyD; 2.00% (0.00-8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10 min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets.
Quantification of run order effect on chromatography - mass spectrometry profiling data J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Izabella Surowiec, Erik Johansson, Hans Stenlund, Solbritt Rantapää-Dahlqvist, Sven Bergström, Johan Normark, Johan Trygg
Chromatographic systems coupled with mass spectrometry detection are widely used in biological studies investigating how levels of biomolecules respond to different internal and external stimuli. Such changes are normally expected to be of low magnitude and therefore all experimental factors that can influence the analysis need to be understood and minimized. Run order effect is commonly observed and constitutes a major challenge in chromatography-mass spectrometry based profiling studies that needs to be addressed before the biological evaluation of measured data is made. So far there is no established consensus, metric or method that quickly estimates the size of this effect. In this paper we demonstrate how orthogonal projections to latent structures (OPLS®) can be used for objective quantification of the run order effect in profiling studies. The quantification metric is expressed as the amount of variation in the experimental data that is correlated to the run order. One of the primary advantages with this approach is that it provides a fast way of quantifying run-order effect for all detected features, not only internal standards. Results obtained from quantification of run order effect as provided by the OPLS can be used in the evaluation of data normalization, support the optimization of analytical protocols and identification of compounds highly influenced by instrumental drift. The application of OPLS for quantification of run order is demonstrated on experimental data from plasma profiling performed on three analytical platforms: GCMS metabolomics, LCMS metabolomics and LCMS lipidomics.
Preparation of phenyl-modified magnetic silica as a selective magnetic solid-phase extraction adsorbent for polycyclic aromatic hydrocarbons in soils J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Shi-Bin Qin, Yu-Han Fan, Xiao-Xuan Mou, Xiao-Shui Li, Shi-Hua Qi
Accurate analysis of polycyclic aromatic hydrocarbons (PAHs) in soils remains a challenge due to the complexity of sample matrices. In this paper, phenyl-modified magnetic mesoporous silica (Fe3O4@mSiO2-Ph-PTSA) was synthesized with p-toluenesulfonic acid (PTSA) as the catalyst and used as a selective adsorbent for the clean-up of PAHs extracted from soils. The material prepared without PTSA as the catalyst (Fe3O4@mSiO2-Ph) was synthesized for comparison. The synthesized materials were first systematically characterized and evaluated. It was found that the grafting amount of the phenyl group onto Fe3O4@mSiO2-Ph-PTSA was higher than that onto Fe3O4@mSiO2-Ph. The extraction efficiency obtained by extracting PAHs from the extracted soil matrix solution demonstrated that Fe3O4@mSiO2-Ph-PTSA possessed a much higher extraction efficiency than that of Fe3O4@mSiO2-Ph, which can be attributed to the greater amount of phenyl groups grafted on Fe3O4@mSiO2 in the presence of the PTSA catalyst. Moreover, contrast experiments showed that Fe3O4@mSiO2-Ph-PTSA displayed higher selectivity towards PAHs than towards n-alkanes and that the π-π interaction played a key role in the adsorption process. In the presence of the soil extract matrix, the parameters affecting the extraction efficiency of Fe3O4@mSiO2-Ph-PTSA for PAHs were optimized. Under the optimal conditions, coupled with pressurized liquid extraction and gas chromatograph-mass spectrometer, the proposed method for the determination of PAHs in soils was linear in the range of 5–500 ng g−1, and the correlation coefficients (R) ranged between 0.9994 and 0.9999. The limits of detection (LODs) and limits of quantification (LOQs), which were based on signal-to-noise ratios of 3 and 10, respectively, were in the range of 0.07–0.41 ng g−1 and 0.24–1.37 ng g−1. The developed method displayed a better clean-up effect than that for silica gel column method, and the matrix effect markedly decreased compared to that of the uncleaned condition. Finally, the developed method was successfully applied for the detection of PAHs in environmental soils, and the data were consistent with the results obtained by the silica gel column method. The analytical results were also consistent with those for the real environment.
A fast and reliable ultrahigh-performance liquid chromatography method to assess the fate of chlorophylls in teas and processed vegetable foodstuff J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Antoni Delpino-Rius, Diana Cosovanu, Jordi Eras, Francesca Vilaró, Mercè Balcells, Ramon Canela-Garayoa
A total of 48 chlorophylls and derivatives were identified and successfully determined in tea and processed vegetable and fruit foodstuff by UHPLC with photodiode-array and mass spectrometry detection. The method allowed the proper separation of chlorophyll derivatives resulting from demetallation, dephytilation, decarbomethoxylation, epimerisation and copperisation. The method was performed in less than 12 min, using an optimised ternary gradient (MeOH, iPrOH, MeCN and H2O with 10 mM of ammonium acetate) on an ACQUITY HSS T3 column. Mass spectrometry, applying both ESI and APCI ionization sources, was used for identification purposes. The method was applied to evaluate the degree of processing in teas of different origin and quality. It allowed differentiation between supermarket own-brand tea bags and teas sold by specialised shops. Pheophytins, pheophorbides and pyro derivatives were found mainly in processed green vegetable and fruit products thereof. However, chlorophyll-derived food colorants, such as Cu-chlorophyllins, Cu-pheophytins, Cu-pyropheophytins, Cu-pheophorbides and Cu-pyropheophorbides, were also detected in several products.
EFFECT OF THE COMBINED USE OF γ-CYCLODEXTRIN AND A CHIRAL IONIC LIQUID ON THE ENANTIOMERIC SEPARATION OF HOMOCYSTEINE BY CAPILLARY ELECTROPHORESIS J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Maider Greño, María Luisa Marina, María Castro-Puyana
The enantioseparation of the non-protein amino acid homocysteine by CE was investigated in this article using eleven neutral CDs and five chiral ionic liquids as chiral selectors. Using a previous derivatization step with FMOC and the subsequent separation under neutral conditions, homocysteine enantiomers were only separated when γ-CD or (R)-N,N,N-trimethyl-2-aminobutanol-bis(trifluoromethane-sulfon)imidate (EtCholNTf2) were employed as sole chiral selectors in the separation buffer. On the one hand, γ-CD gave rise to the enantiomeric separation in 10 min with a resolution value of 1.9, whereas EtCholNTf2 let to obtain a resolution value of 1.4 in more than 50 min. Then, the evaluation of the combined use of both selectors was also carried out, resulting in a considerable increase in the Rs. The best enantioseparation for homocysteine was obtained when 10 mM EtCholNTf2 was added to 50 mM phosphate buffer (pH 7.0) containing 2 mM γ-CD. In an attempt to discriminate specific chiral cation effect from the salt effect, the influence of adding LiNTf2 to the separation medium was also evaluated, resulting in lower resolution values for homocysteine when compared to those achieved with the addition of EtCholNTf2, indicating a synergistic effect between EtCholNTf2 and γ-CD. Interestingly, the enantiomer migration order changed depending on the use of a single chiral selector or dual systems. When EtCholNTf2 or γ-CD were employed as sole chiral selectors, D-enantiomer was the first-migrating enantiomer. However, an inversion in the migration order was observed when both selectors were combined in a dual system being the L-enantiomer the first-migrating one.
An untargeted lipidomic strategy combining comprehensive two-dimensional liquid chromatography and chemometric analysis J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Meritxell Navarro-Reig, Joaquim Jaumot, Romà Tauler
Untargeted lipidomic samples are extremely complex and often exceed the limits of peak capacity achievable by one-dimensional liquid chromatography (LC). Comprehensive two-dimensional liquid chromatography (LC × LC) appears as a promising alternative to overcome this drawback. Unfortunately, this approach generates highly complex datasets which untargeted analysis is challenging. In this work, a global methodological strategy combining LC × LC-MS with chemometric data analysis is proposed for untargeted lipidomic studies. The feasibility of the proposed methodology is demonstrated by its application to assess the effects of arsenic exposure on the lipidome of growing rice samples. A two-dimensional chromatographic setup coupling reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC) modes together with a triple quadrupole mass detector (TQD) is proposed to analyze lipid extracts from rice samples at different experimental conditions. Chemometric tools were used for data compression, spectral and elution profiles resolution, feature detection and statistical analysis of the multidimensional LC × LC data. The obtained results revealed that the proposed methodology was useful to gather relevant information from untargeted lipidomic studies and detect potential biomarkers.
Development of an advanced derivatization protocol for the unambiguous identification of monosaccharides in complex mixtures by gas and liquid chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-05 Maren Haas, Saskia Lamour, Oliver Trapp
The separation and analysis of complex monosaccharide mixtures is highly challenging and requires typically carefully selected derivatization procedures to avoid changes in the sample composition. Here we present in a comparative study several single- and two-step derivatization approaches for LC and GC separations using a set of reference compounds ranging from C1 building block such as formaldehyde to C6 monosaccharides. Separation conditions have been optimized resulting in the simultaneous separation of 15 unbranched aldoses. By parallel derivatization using hydroxylamine hydrochloride (HACl)/ N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and O-ethylhydroxylamine hydrochloride (EtOx)/ N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and comparative GC measurements we developed a protocol for the unambiguous identification and separation of aldoses, ketoses, alditols and aldonic acids, which commonly occur in complex sugar mixtures as reaction by-products or decomposition products. In particular this procedure helps to deconvolute overlapping analytes and facilitates quantification. Additionally, the method presented here has been investigated in regard to storage life, detection limits, quantification and MS analysis. The broad applicability of this method to different sample matrices is shown for the analysis of food samples and complex aldol reaction mixtures in the formose reaction, which is of great relevance in the context of the origin of life.
Multi-residue enantiomeric analysis of 18 chiral pesticides in water, soil and river sediment using magnetic solid-phase extraction based on amino modified multiwalled carbon nanotubes and chiral liquid chromatography coupled with tandem mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-06 Pengfei Zhao, Zhaokun Wang, Kunjie Li, Xingjie Guo, Longshan Zhao
This manuscript describes, for the first time, the multi-residue analysis of 18 chiral pesticides at enantiomeric levels in both environmental liquid (river water, influent and effluent wastewater) and solid matrices (agricultural soil, forestal soil and river sediment) based on magnetic solid-phase extraction (MSPE) and chiral liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Magnetic amino modified multiwalled carbon nanotubes (m-MWCNTs-NH2) were prepared and firstly applied to adsorb pesticides from complex matrices. Response surface methodology (RSM) was applied to assist the multivariable optimization. The simultaneous enantioseparation of the chiral pesticides was performed on a Chiralpak IG column. Under the optimum conditions, the mean recoveries for pesticides enantiomers from the water matrices ranged from 81.1 to 106.3% with intra-day RSD of 2.1-11.9% and inter-day RSD of 2.6-12.7%; the mean recoveries for all enantiomers from the solid matrices ranged from 80.3 to 105.9% with intra-day RSD of 2.3-10.9% and inter-day RSD of 4.0-13.4%. Good linearity was achieved for all enantiomers with determination coefficients ( r2) greater than 0.9912. Method quantification limits were below 2.04 ng L-1 in liquid matrices and below 0.50 ng g-1 in solid matrices. The developed method offered some advantages, such as simple operation, rapidity and high concentration factor. Therefore, it is suitable for monitoring the enantiomeric compositions of chiral pesticides in different environmental matrices.
Evaluation of chromatofocusing as a capture method for monoclonal antibody products J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-06 Yang Liu, Sevda Deldari, Hui Guo, Chittoor R. Narahari, Ronald C. Bates, Ryan Swanson, Sanchayita Ghose, Zheng Jian Li, Douglas D. Frey
Chromatofocusing is investigated as an alternative to protein A chromatography for the initial capture step in a purification process for several monoclonal antibodies and antibody fusion products. For comparison, this work also investigates the use of ion-exchange chromatography with either pH or salt gradient elution as additional alternatives to protein A chromatography. The specific conditions employed for the capture step for the case of chromatofocusing were selected on a rational basis using a computer-aided design method implemented in the form of a Microsoft Excel spreadsheet. Alternative operating conditions were compared experimentally with regard to the product yield achieved as well as the removal of total host cell proteins (HCPs) and of a specific HCP major component. Results from this study indicate that both chromatofocusing and ion-exchange chromatography are useful alternatives to a protein A chromatography capture step in many practical cases. This is especially true for the case of chromatofocusing when it is possible to exploit the ability of the method to create complex gradient shapes that are self-forming inside the column and to simultaneous focus and separate proteins inside the column.
Development of a Retention Time Interpolation scale (RTi) for liquid chromatography coupled to mass spectrometry in both positive and negative ionization modes J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-06 Alberto Celma, Lubertus Bijlsma, Francisco J. López, Juan V. Sancho
The accuracy and sensitivity of high resolution mass spectrometry (HRMS) enables the identification of candidate compounds with the use of mass spectrometric databases among other tools. However, retention time (RT) data in identification workflows has been sparingly used since it could be strongly affected by matrix or chromatographic performance. Retention time interpolation scaling (RTi) strategies can provide a more robust and valuable information than RT, gaining more confidence in the identification of candidate compounds in comparison to an analytical standard. Up to our knowledge, no RTi has been developed for LC-HRMS systems providing information when acquiring in either positive or negative ionization modes.In this work, an RTi strategy was developed by means of the use of 16 isotopically labelled reference standards, which can be spiked into a real sample without resulting in possible false positives or negatives. For testing the RTi performance, a mixture of several reference standards, emulating suspect analytes, were used. RTi values for these compounds were calculated both in solvent and spiked in a real matrix to assess the effect of either chromatographic parameters or matrix in different scenarios. It has been demonstrated that the variation of injection volume, chromatographic gradient and initial percentage of organic solvent injected does not considerably affect RTi calculation. Column aging and solid support of the stationary phase of the column, however, showed strong effects on the elution of several test compounds. Yet, RTi permitted the correction of elution shifts of most compounds. Furthermore, RTi was tested in 47 different matrices from food, biological, animal feeding and environmental origin. The application of RTi in both positive and negative ionization modes showed in general satisfactory results for most matrices studied.The RTi developed can be used in future LC-HRMS screening analysis giving an additional parameter, which facilitates tedious processing tasks and gain more confidence in the identification of (non)-suspect analytes.
Magnetic beads-based neuraminidase enzyme microreactor as a drug discovery tool for screening inhibitors from compound libraries and fishing ligands from natural products J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-06 Yu-Mei Zhao, Lv-Huan Wang, Si-Fan Luo, Qi-Qin Wang, Ruin Moaddel, Ting-Ting Zhang, Zheng-Jin Jiang
Neuraminidase (NA) is a glycoside hydrolase that has been proposed as a potential therapeutic target for influenza. Thus, the identification of compounds that modulate NA activity could be of great therapeutic importance. The aim of this study is to develop a drug discovery tool for the identification of novel modulators of NA from both compound libraries and natural plant extracts. NA was immobilized onto the surface of magnetic beads and the inherent catalytic activity of NA-functionalized magnetic beads was characterized. Based on the enzymatic activity (hydrolysis ratio), the inhibitory activities of 12 compounds from plant secondary metabolites were screened, and the desired anti-NA activities of flavonoids were certified. Ligand fishing with the immobilized enzyme was optimized using an artificial test mixture consisting of oseltamivir, lycorine and matrine prior to carrying out the proof-of-concept experiment with the crude extract of Flos Lonicerae. The combination of ligand fishing and HPLC-MS/MS identified luteolin-7-O-β-D-glucoside, luteolin, 3,5-di-O-caffeoylquinic acid and 3,4-di-O-caffeoylquinic acid as neuraminidase inhibitory ligands in Flos Lonicerae. This is the first report on the use of neuraminidase functionalized magnetic beads for the identification of active ligands from a botanical matrix, and it sets the basis for the de novo identification of NA modulators from complex biological mixtures.
Characterization of radial and axial heterogeneities of chromatographic columns by flow reversal J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Fabrice Gritti, Mike Dion, Attila Felinger, Mike Savaria
The impact of the column length (5, 10, and 15 cm) and packing mode (constant pressure and constant flow rate up to 15,000 psi) on the radial and axial heterogeneities of 3.0 mm i.d. research prototype columns packed with the same batch of 2.4 μm BEH-C18 particles was investigated by the flow reversal technique. The data were gathered for a non-retained marker (uracil, acetonitrile/water eluent mixture, 80/20, v/v, flow rate 0.5 mL/min, T=297 K) and revealed that the radial heterogeneity of the packed bed, characterized by the center-to-wall relative velocity bias (ωβ) and its length scale, is nearly independent on the packing mode: the velocity biases extend over a same length scale estimated at 154 μm while ωβ is in between 4% and 6% for all columns. Secondly, the data revealed that the column length has a slight impact on ωβ: assuming a two-region (wall and center regions) stochastic model of transcolumn eddy dispersion, ωβ increases from 4.6% to 5.1% and to 6.1% for 5, 10, and 15 cm long columns, respectively, when packed at constant flow rate. For columns packed at constant pressure, ωβ increases from 5.0% to 5.2% and to 5.6%, respectively. Finally, it is found that all columns are axially heterogeneous: the bottom half, which is packed first (column inlet), is slightly more uniform than the top half (column outlet) which is packed last. Overall, the results of the flow reversal experiments corroborate recent observations (130 μm thick wall region and ωβ=5.0%) based on flow simulations in a focused-ion-beam scanning electron microscopy (FIB-SEM) based 3D reconstruction from a 2.1 mm × 50 mm column packed with 2 μm BEH-C18 particles.
Direct chromatographic study of the enantioselective biodegradation of ibuprofen and ketoprofen by an activated sludge J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Laura Escuder-Gilabert, Yolanda Martín-Biosca, Mireia Perez-Baeza, Salvador Sagrado, María José Medina-Hernández
The quantification of the enantiomeric fraction (EF) during the biodegradation process is essential for environmental risk assessment. In this paper the enantioselective biodegradation of ibuprofen, IBU, and ketoprofen, KET, two of the drugs most consumed, was evaluated. Biodegradation experiments were performed in batch mode using a minimal salts medium inoculated with an activated sludge (collected from a Valencian Waste Water Treatment Plant) and supplemented with the racemate of each compound. The inoculum activity was verified using fluoxetine as reference compound. The experimental conditions used (analyte concentration and volume of inoculum) were chosen according to OECD guidelines. In parallel, the optical density at 600 nm was measured to control the biomass growth and to connect it with enantioselectivity. Two RPLC methods for chiral separations of IBU and KET using polysaccharides-based stationary phases were developed. Novel calculations and adapted models, using directly the chromatographic peak areas as dependent variable, were proposed to estimate significant parameters related to the biodegradation process: biodegradation (BD) and EF values at given time, half-life times of (R)- and (S)-enantiomers, number of days to reach a complete BD and the minimum EF expected. The modelled BD and EF curves fitted adequately the data (R2 > 0.94). The use of these new equations provided similar results to those obtained using concentration data. However, the use of chromatographic peak areas data, eliminates the uncertainty associated to the use of the calibration curves. The results obtained in this paper indicate that an enantiorecognition towards IBU enantiomers by the microorganisms present in the activated sludge used in this study occurred, being the biodegradation of (R)-IBU higher than that of (S)-IBU. For KET, non-enantioselective biodegradation was observed.
Activation of Resin with Controllable Ligand Density via Catalytic oxa-Michael Addition and Application in Antibody Purification J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Fang Cheng, Mingyang Li, Wei He, Bingbing Sun, Jinyan Qin, Jingping Qu
This article reported a new strategy for resin activation with divinyl sulfone using catalytic oxa-Michael addition in a controllable manner. By screening a variety of organocatalysts, PPh3 and DMAP stand out with high catalytic efficiency in aprotic solutions. X-ray photoelectron spectroscopy (XPS) analysis indicates high reaction efficiency and less side reactions than traditional aqueous reactions, resulting in high activation density. A maximum activation density of 157.5 ± 1.2 μmol/g resin was achieved in 12 h using PPh3 as catalyst, which is 1.5 times higher than the traditional aqueous reactions. Followed by conjugation with a chromatographic ligand, i.e., 4-mercaptoethyl pyridine (MEP), the resin is capable of antibody purification. Using IgG and BSA as model proteins, adsorption isotherms and dynamic binding behavior of the resin samples were investigated. A higher affinity and dynamic binding capacity of IgG was observed on resins with higher ligand density. Finally, the resin samples were applied to the purification of a therapeutic monoclonal antibody from cell culture supernatant. The recovery of the resin samples with high ligand density are 70% higher than those of the commercial resin (MEP HyperCel). Moreover, our method achieves a controllable chromatographic ligand density by varying reaction times, which is useful to clarify the density-affinity relationship and improve process-scale antibody purification.
Purification and enrichment of polycyclic aromatic hydrocarbons in environmental water samples by column clean-up coupled with continuous flow single drop microextraction J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Yue Li, Lening Zhang, Lijie Wu, Shuang Sun, Hongyan Shan, Ziming Wang
A novel method for the determination of sixteen polycyclic aromatic hydrocarbons (PAHs) in environmental water samples was developed using column clean-up (CCU) coupled with continuous flow single drop microextraction (CF-SDME) prior to the determination by gas chromatography-mass spectrometry (GC-MS). In this method, purification, extraction and enrichment were carried out in a single step, which reduced the effect of most organic interferents on the determination of target analytes, greatly simplified the operation process and shortened the whole pre-treatment time. The CCU-CF-SDME system was first used, and shortcomings such as long extraction time, instability of suspended microdrop of the traditional SDME system were overcome. The influences of several experimental parameters, including the type and amount of column packing material, the type and volume of extraction solvent, the flow rate of sample solution, extraction temperature, pH and ionic strength of sample solution, on the extraction efficiency were investigated. Under the optimal experimental conditions, the good linearities were obtained in the concentration range of 0.02–10 μg L-1 with correlation coefficients ranging from 0.9912 to 0.9995 for all the analytes. The limits of detection and quantification of the analytes were in the range of 0.0012–0.0101 µg L-1 and 0.0041–0.0336 μg L-1, respectively. The pre-concentration factors in the range of 777–978 for the PAHs were obtained. The proposed method was applied on the analysis of environmental water samples, and the recoveries of target analytes were in the range of 81.8–105.8% with the relative standard deviations ranging from 0.5% to 6.4%. The results showed that the developed method was a simple, quick and feasible method for the determination of PAHs in environmental water samples.
Development and validation of a method for direct, underivatized analysis of free amino acids in rice using liquid chromatography-tandem mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 G.V.V. Liyanaarachchi, K.R.R. Mahanama, H.P.P.S. Somasiri, P.A.N. Punyasiri
Inspired by the apparent relationship of free amino acids (FAAs) which are present in minute quantities with the organoleptic characteristics of food,- there is an increased demand for analytical methods sensitive in trace level detection. This study presents the validation results of a simple and rapid method developed for direct, underivatized analysis of FAAs in rice using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI).The method demonstrated satisfactory selectivity for twenty FAAs with minimum matrix effect. The recoveries obtained for samples fortified at three concentration levels: low mid and high, covering the working range of the method were in the range 80% - 110%. The precision measured in terms of repeatability and reproducibility of the method expressed as percentage relative standard deviation (% RSD) were below 10% for the amino acids analyzed. The detection limits (LODs) and quantification limits (LOQs) of the method were in the range 0.4 -1.0 mg/kg and 0.6 – 1.2 mg/kg respectively. Method had a wide linear range between 1.25-100 mg/kg with regression coefficients greater than 0.999 obtained over seven calibration levels. The method was also found robust over other cereals including corn, wheat and finger millet with satisfactory recoveries and precision values. The percentage expanded uncertainties calculated with the coverage factor of 2 (k = 2), were below 14% for the analyzed amino acids.The developed, simple and rapid LC-MS/MS method is accurate and reproducible, allowing determination of underivatized FAAs in rice and comply with the international method validation guideline requirements.
Direct injection analysis of polar micropollutants in natural drinking water sources with biphenyl liquid chromatography coupled to high-resolution time-of-flight mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Vittorio Albergamo, Rick Helmus, Pim de Voogt
A method for the trace analysis of polar micropollutants (MPs) by direct injection of surface water and groundwater was validated with ultrahigh-performance liquid chromatography using a core-shell biphenyl stationary phase coupled to time-of-flight high-resolution mass spectrometry. The validation was successfully conducted with 33 polar MPs representative for several classes of emerging contaminants. Identification and quantification were achieved by semi-automated processing of full-scan and data-independent acquisition MS/MS spectra. In most cases good linearity (R2 ≥ 0.99), recovery (75% to 125%) and intra-day (RSD < 20%) and inter-day precision (RSD < 10%) values were observed. Detection limits of 9 to 83 ng/L and 9 to 93 ng/L could be achieved in riverbank filtrate and surface water, respectively. A solid-phase extraction was additionally validated to screen samples from full-scale reverse osmosis drinking water treatment at sub-ng/L levels and overall satisfactory analytical performance parameters were observed for RBF and reverse osmosis permeate. Applicability of the direct injection method is shown for surface water and riverbank filtrate samples from an actual drinking water source. Several targets linkable to incomplete removal in wastewater treatment and farming activities were detected and quantified in concentrations between 28 ng/L for saccharine in riverbank filtrate and up to 1 µg/L for acesulfame in surface water. The solid phase extraction method applied to samples from full-scale reverse osmosis drinking water treatment plant led to quantification of 8 targets between 6 and 57 ng/L in the feed water, whereas only diglyme was detected and quantified in reverse osmosis permeate. Our study shows that combining the chromatographic resolution of biphenyl stationary phase with the performance of time-of-flight high-resolution tandem mass spectrometry resulted in a fast, accurate and robust method to monitor polar MPs in source waters by direct injection with high efficiency.
Axial heterogeneities in capillary ultrahigh pressure liquid chromatography columns: Chromatographic and bed morphological characterization J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-07 Arved E. Reising, Justin M. Godinho, Janek Bernzen, James W. Jorgenson, Ulrich Tallarek
We study axial heterogeneities in capillary ultrahigh pressure liquid chromatography (UHPLC) columns through kinetic performance and bed morphological analysis. Two columns are used in this work, a 75 µm i.d. × 100 cm column packed with 1.3 µm C18-silica particles and a 75 µm i.d. × 45 cm column packed with 1.9 µm C18-silica particles. The long column is chromatographically characterized and is afterwards sectioned into three segments, each analyzed individually. The column packed with the 1.9 µm particles is subjected to a bed morphological analysis using confocal laser scanning microscopy near the inlet, center, and outlet of the column. Chromatographic and morphological characterizations reveal highest separation efficiency and most homogeneous bed microstructure towards the column outlet. Kinetic performance data for inlet and central packing segments indicate enhanced contributions from wall effects to a transcolumn flow heterogeneity. Bed morphological data reveal systematic changes in geometrical and frictional wall effects along the bed: from inlet to outlet, bed morphologies increasingly reflect packing microstructures associated with concentrated slurries. Variations in separation efficiency and bed morphology can be related to the constant-pressure packing mode; the decrease in packing rate along the bed leaves fewer chances for particle rearrangement and bed consolidation from inlet to outlet. It explains the relatively uniform bed morphology towards the outlet and also the relatively loose wall region near the inlet. Bed microstructural features are discussed in a context of previous observations made in the characterization of capillary UHPLC columns.
Metabolomic Analysis of Mammalian Cells and Human Tissue through One-Pot Two Stage Derivatizations using Sheathless Capillary Electrophoresis-Electrospray Ionization-Mass Spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-04 Tianjiao Huang, Michael Armbruster, Richard Lee, Dawn S. Hui, James L. Edwards
Analysis of metabolites is often performed using separations coupled to mass spectrometry which is challenging due to their vast structural heterogeneity and variable charge states. Metabolites are often separated based on their class/functional group which in large part determine their acidity or basicity. This charge state dictates the ionization mode and efficiency of the molecule. To improve the sensitivity and expand the coverage of the mammalian metabolome, multifunctional derivatization with sheathless CE-ESI-MS was undertaken. In this work, amines, hydroxyls and carboxylates were labeled with tertiary amines tags. This derivatization was performed in under 100 minutes and resulted in high positive charge states for all analytes investigated. Amino acids and organic acids showed average limits of detection of 76 nM with good linearity of 0.96 and 10% RSD for peak area. Applying this metabolomic profiling system to bovine aortic endothelial cells showed changes in 15 metabolites after treatment with high glucose. The sample injection volume on-capillary was <300 cells for quantitative analyses. Targeted metabolites were found in human tissue, which indicates possible application of the system complex metabolome quantitation.
Qualitative and quantitative comparison of cyclic phosphatidic acid and its related lipid species in rat serum using hydrophilic interaction liquid chromatography with tandem-mass spectrometry J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-04 Keiko Fukasawa, Shingo Nakajima, Mari Gotoh, Seiya Tanaka, Hiromu Murofushi, Kimiko Murakami-Murofushi
Cyclic phosphatidic acid (cPA) is a simple lipid containing a fatty acid attached at the sn-1 position and a cyclic phosphate ring structure at the sn-2 and sn-3 positions of the glycerol backbone. The pharmacological effects of cPA have been demonstrated in several diseases such as cancer and neuropathic pain; however, the composition of the molecular species of cPA in relative to other lipid species in biological samples is still unclear. Recently, hydrophilic interaction liquid chromatography (HILIC) has demonstrated the ability to perform lipidomic analyses of biological samples. In the present study, we developed the quantitative measurement of cPA and its related lipid species, such as lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC), in rat serum using HILIC equipped with tandem-mass spectrometry (MS/MS). The lipid analysis using HILIC-MS/MS system demonstrated high linearity and reproducibility. The modified Bligh and Dyer method using citric acid was showed high efficiency on the extraction of cPA and LPA without contamination of artificial products. In rat serum, cPA and LPC contained more saturated fatty acids such as palmitic acid and stearic acid than unsaturated fatty acids, whereas LPA and phosphatidylcholine more contained unsaturated fatty acids than saturated fatty acids. The analytical methods for measuring cPA and its related lipid species in the present study will aid the analysis of their metabolism.
Direct bioautography hyphenated to direct analysis in real time mass spectrometry: Chromatographic separation, bioassay and mass spectra, all in the same sample run J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 Tim T. Häbe, Maryam Jamshidi-Aidji, Jennifer Macho, Gertrud E. Morlock
Mass spectra were recorded directly in situ the bioautogram, i.e., in the presence of micro-organisms, bioassay medium and substrate reagent. The desorption-based direct analysis in real time mass spectrometry (DART-MS) was applied immediately after direct bioautography (DB). It turned out to be an advantageous combination, as it offered the possibility of a straightforward mass spectrometric detection of bioactive analytes within the bioautogram, and at the same time, it was discriminating microorganism cells and highly polar bioassay medium ingredients which could otherwise stress the MS system. DB-DART-MS was investigated for bioactive compounds in cosmetics using the Bacillus subtilis and Aliivibrio fischeri bioassays for detection of Gram-positive and Gram-negative antimicrobials, respectively, and the planar yeast estrogen screen for detection of estrogen-effective compounds. The influences of the three different bioassay matrices on the analyte response and DB-DART-MS performance on different layers were studied on the example of parabens in hand creams. It was shown that with increasing culture medium complexity, the ion suppression increased. As proof-of-principle, the mass spectro-metric quantification at the nanogram level in situ the bioautogram was verified by comparison to HPTLC-DART-MS. The total paraben contents of hand creams 1 and 2 were 0.17–0.20% and 0.30–0.34%, respectively, depending on the method used (DB-DART-MS with two different bioassays or HPTLC-DART-MS as well as on RPW or NP plate). In contrast to the current practice of applying the sample twice and subjecting one track to the bioassay and another to MS, the introduced hyphenation DB-DART-MS is straightforward and highly efficient.
Separation of highly charged compounds using competing ions with hydrophilic interaction liquid chromatography – Application to assay of cellular nucleotides J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 Amitha K. Hewavitharana, Vicrant Narayan, John A. Duley
Separation of highly charged compounds has always been a challenge in chromatography. Ion-pair reversed phase chromatography has been the most successful approach to date. Although polar reversed phase and HILIC columns have been introduced, they have limitations with highly charged compounds. Competing ions have been used, in addition to ion-pair reagent, to achieve better resolution with reversed phase columns. Herein, we explored the use of competing ions with HILIC columns to demonstrate the effects on retention and separation of mono-, di-, and tri-nucleotides, introducing a new tool to improve resolution with HILIC columns. HILIC columns that had irreversibly retained highly charged tri-nucleotides became capable of successfully separating the same compounds, by using this approach. The optimised method was used to successfully resolve a mixture of 12 nucleotides with charges ranging from 1- to 3-. The method was applied to quantify nucleotides in blood cell extracts.
Melamine-based porous organic polymers inline solid phase extraction coupled with high performance liquid chromatography for the analysis of phytohormones in juice samples J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 Sijie Zheng, Man He, Beibei Chen, Bin Hu
A melamine-based porous organic polymer (mPMF) was synthesized as solid phase extraction (SPE) adsorbent for inline SPE-high performance liquid chromatography (HPLC)-ultraviolet detector (UV) analysis of five phytohormones. Melamine contributed to the rich π-electron and N-containing triazine structure for mPMF, which could form π-π interaction and intermolecular hydrogen bond with -COOH containing phytohormones. The synthesized mPMF adsorbent shows extremely high extraction efficiency for five target analytes (>80%) including salicylic acid, indole-3-acetic acid, abscisic acid, 2,4-dichlorophenoxyacetic acid and 1-naphthalene acetic acid. The factors affecting extraction of the target phytohormones were investigated and the optimized experimental conditions were established. The linear range was 0.2-100 μg/L with the limits of detection in the range of 0.06-0.11 μg/L for five target phytohormones. The developed method of mPMF-inline-SPE-HPLC-UV was applied for the analysis of trace target phytohormones in tomato and grape juice samples, and the recovery in the range of 83.1-116% and 87.2-121% was obtained for the spiked tomato and grape juice, respectively. This method has the advantages of high sensitivity and good reproducibility, and it has good application potential for the analysis of phytohormones in fruit samples. Moreover, inline analysis avoided the problems of sample pollution and sample loss, and provided a sample throughput of 5/h.
Modified binodal model describes phase separation in aqueous two-phase systems in terms of the effects of phase-forming components on the solvent features of water J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 L.A. Ferreira, V.N. Uversky, B.Y. Zaslavsky
The binodal model pioneered by Guan et al. [Y. Guan, T. H. Lilley, T. E. Treffry, J. Chem. Soc. Faraday Trans., 89 (1993) 4283-4298] remains the most successful in regard to the quantitative description of phase diagrams among various theoretical models proposed to describe phase separation in aqueous mixtures of polymers. This is a semi-empirical model based on the assumption that any point on the binodal line may be viewed as a saturated solution of the phase-forming compound-1 in the solution of the phase-forming compound-2. Although this model is originally based on the excluded volume concept, we suggest that the solubility of the compound-1 in solutions of compound-2 may depend on the solvent properties of water in solutions of compound-2. The binodal model described in these terms was very successfully applied to the phase diagrams of aqueous two-phase systems formed by different pairs of polymers (dextran, Ficoll, poly(ethylene glycol)-8000, and Ucon). Phase diagram of a new aqueous two-phase system formed by trimethylamine N-oxide (TMAO) and polypopylene glycol-400 and previously reported phase diagram for system formed by TMAO and poly(ethylene glycol)-600 were also described by this model quite well. It was found that the modified binodal model is also applicable to single polymer-salt and polymer-ionic liquid aqueous two-phase systems. The most important conclusion of our study is that the effects of different compounds (polymers, salts, ionic liquids) on the solvent features of water in their aqueous solutions cause changes in the water structure, resulting in phase separation in the mixtures of these compounds.
Removal of bias in C37 alkenone-based sea surface temperature measurements by high-performance liquid chromatography fractionation J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 Oscar Rama-Corredor, Aleix Cortina, Belen Martrat Jordi F. Lopez, Joan O. Grimalt
Sea surface temperature determinations based on marine sedimentary C37 alkenone distributions have provided a wealth of data for paleoclimatic studies, including those performed at high resolution. The success of this approach results from several characteristics of alkenone compounds, e.g. their geochemical properties (such as unequivocal synthesis by certain widespread haptophyte algae, plus chemical stability/preservation of the original alkenone distributions during sedimentation), and their analytical properties (such as fast clean up procedures using alkaline hydrolysis of sediment extracts, followed by robust instrumental methods allowing large scale sample processing). Here we show that, in sediments under the influence of continental inputs, coelution of these compounds with cholest-5-enyl 3β-undecenyl ether and 24-methylcholesta-5,22-dienyl 3β-undecenyl ether deviate the SST measurements despite alkaline hydrolysis. Here, we report a new high performance liquid chromatrography fractionation method which eliminates these interfering compounds and gathers all the alkenones into a single fraction. These fractions can then be analysed by gas chromatography as in the initial approach, providing large amounts of data as required in high resolution studies.
Hexagonal boron nitride stationary phase for gas chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-03 Xue Xiong, Meiling Qi
This work describes the separation performance of utilizing hexagonal boron nitride (h-BN) as the stationary phase for capillary gas chromatography (GC). The statically coated h-BN column showed moderate polarity and achieved column efficiencies of 3455 plates/m and 3800 plates/m for naphthalene and n-dodecane, respectively. With temperature-dependent structure properties, the h-BN stationary phase exhibited stronger retention for polycyclic aromatic hydrocarbons (PAHs) over phthalic acid esters (PAEs) and showed advantageous separation performance over the g-C3N4 and commercial polysiloxane stationary phases. Moreover, it displayed preferential retention for halogenated analytes and high resolution performance for structural and positional isomers. In addition, the h-BN column showed good column repeatability with relative standard deviation (RSD) values of 0.03% - 0.07% for run-to-run, 0.31% - 0.71% for day-to-day and 2.6% - 5.3% for column-to-column, respectively, and thermal stability up to 260 °C.
Preparation of porous zinc ferrite/carbon as a magnetic-assisted dispersive miniaturized solid phase extraction sorbent and its application J. Chromatogr. A (IF 3.716) Pub Date : 2018-07-02 Shujun Xia, Zhixiong Cai, Jing Dong, Shuya Wang, Yiru Wang, Huaizhi Kang, Xi Chen
In this study, porous ZnFe2O4/carbon, derived from Zn-Fe zeolitic imidazolate framework (Zn-Fe-ZIF), was employed as a novel sorbent for magnetic-assisted dispersive miniaturized solid phase extraction (M-DµSPE). The Zn-Fe-ZIF derived magnetic porous ZnFe2O4/carbon was easily prepared using a one-pot solvothermal method, and its morphology, structure and magnetic characteristics were evaluated via scanning electron microscopy, powder X-ray diffraction, Raman spectroscopy and vibrating sample magnetometry. The extraction ability of ZnFe2O4/carbon is evaluated by different kinds of compounds including organochlorine pesticides, pyrethroid insecticides, aldehydes, nerolidol, benzoic acid and sorbic acid. A M-DµSPE method was developed for the analysis of organochlorine pesticides. Several parameters affecting the extraction efficiency were systematically investigated. The calibration curves ranged from 0.05 to 100 ng g-1 and the limits of detection were 0.005-0.3 ng g-1. The intra-day and inter-day relative standard deviations were lower than 2.3 and 5.2%. The recoveries of spiked organochlorine pesticides were in the range of 86.1-109.4%.
Separation and identification of phospholipids by hydrophilic interaction liquid chromatography coupled to tandem high resolution mass spectrometry with focus on isomeric phosphytidylglycerol and bis(monoacylglycero)phosphate J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-30 Christian Vosse, Carina Wienken, Cristina Cadenas, Heiko Hayen
Changes in lipid composition of cells or tissue are often linked to various diseases. Studies indicate alterations of bis(monoacylglycero)phosphate (BMP) species in diseases such as cancer. Therefore, an extended phospholipid profiling method based on hydrophilic interaction liquid chromatography (HILIC) coupled to high-resolution mass spectrometry (MS) and data-dependent MS/MS acquisition was developed to separate and unambiguously identify BMP species. Lipid species identification was based on retention time, accurate mass and specific MS/MS fragments. The developed method was applied in a proof of concept study to lipid extracts of a cell culture model of conditional oncogene overexpression in MCF-7/NeuT breast cancer cells. Comparison of control and oncogene-induced MCF-7/NeuT breast cancer cells showed changes in BMP species distribution. Thereby, a shift from long-chain to shorter-chain fatty acid composition in BMP species was detected.
Resolution and signal-to-noise in analysis of carbohydrate isomers by graphitised carbon chromatography with charged aerosol detection J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-30 Aleksander Lie, Lars Haastrup Pedersen
The effects of co-eluents and additives on separation and signal-to–noise ratio in analyses of monosaccharides by graphitised carbon chromatography (GCC) in combination with charged aerosol detection were studied. Design of experiments was used to model and predict the elution of two monosaccharide isomers, galactose and glucose and the corresponding amine at varying isocratic conditions, including concentration of water-soluble co-eluent, flow and temperature. The study confirmed the well-known order of eluent strength of the co-eluents investigated but showed that the eluent strength of MeOH was significantly lower than that of ACN, and at co-eluent concentrations ≥ 5 % (v/v) IPA approached that of THF. Addition of NH3 increased retention and improved both peak shape and separation but the detector response decreased with increasing NH3 concentration lowering the signal-to-noise ratio. The best combination of response, retention and separation was obtained at 0.1 % NH3. Increasing column temperature in the range of 15 – 50 °C resulted in decreased retention times and resolution. The corresponding Van’t Hoff correlations showed negative adsorption enthalpies indicating an exothermic adsorption process driven by a decrease in entropy minimising the surface energy of the system. Isocratic elution with MeOH as co-eluent offered limited possibilities for optimisation of resolution due to the opposite effects of changes in co-eluent concentration and changes in flow rate. Elution with acetonitrile as co-eluent showed possibilities for optimisation of the resolution within the range of flow rates of 0.6-0.95 mL/min and co-eluent concentrations of 0.1–0.3 %, with the highest resolution predicted at 0.1 % acetonitrile and a flow rate of 0.81 mL/min. Saccharides in the size range DP1-4, including amino, acetamido, and deoxy sugars, were separated using a binary gradient method. Higher retention was observed for increasing degree of polymerisation (DP) and N-acetylated saccharides were retained longer than non-substituted saccharides of corresponding DP. Partial resolution of two lacto-N-tetrasaccharide positional isomers was obtained.
Facile synthesis of magnetic covalent organic framework nanobeads and application to magnetic solid-phase extraction of trace estrogens from human urine J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-28 Lei Chen, Mingyue Zhang, Fengfu Fu, Jingguang Li, Zian Lin
A rapid and facile approach was developed for the synthesis of core-shell structured magnetic covalent organic framework nanobeads by using the monodisperse Fe3O4 nanoparticles (NPs) as magnetic core, and 1,3,5-triformylbenzene (Tb) and benzidine (Bd) as two building blocks (denoted as Fe3O4@TbBd), which were explored as an adsorbent for magnetic solid-phase extraction (MSPE) of estrogens from human urine sample. The core-shell structured Fe3O4@TbBd nanobeads showed some attractive features involving high specific surface area (202.18 m2/g), uniform pore size distribution (2.8 nm), high magnetic responsivity (41.4 emu/g), as well as excellent thermal and chemical stability, which made it an ideal adsorbent for selective isolation and enrichment of estrogens. Some parameters influencing extraction efficiency, including adsorbent dosage, extraction time, pH, ion strength, desorption solvent and desorption time were investigated systematically. Combined with HPLC–MS, a simple, fast, and sensitive method was developed for the enrichment and sensitive determination of seven estrogens, which showed good linearity (r > 0.9978) in the range of 0.005–10 μg/L, low limits of detection (0.2–7.7 ng/L, S/N = 3), low limits of quantification (0.6–25.6 ng/L, S/N = 10), high enrichment factors (75–197 fold), and good precision with relative standard deviations (RSD) lower than 4.8% for intra-day and 6.7% for inter-day. The proposed method was successfully applied to the analysis of trace estrogens in urine sample of pregnant woman with good recoveries (80.6–111.6%), demonstrating the promising potential of the Fe3O4@TbBd nanobeads as adsorbent in sample pretreatment.
Quantification of inorganic anions and organic acids in apple and orange juices using novel covalently-bonded hyperbranched anion exchanger with improved selectivity J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-28 A.S. Uzhel, A.V. Zatirakha, A.D. Smolenkov, O.A. Shpigun
Chromatographic analysis of orange and apple juices is provided using novel covalently-bonded poly(styrene-divinylbenzene)-based (PS-DVB) hyperbranched anion exchanger for suppressed ion chromatography (IC) with improved selectivity toward inorganic anions and organic acids. The obtained stationary phase provides baseline resolution of weakly retained organic acids such as glycolate, acetate, lactate, and formate, which are not separated to baseline with modern commercially available anion exchangers. The proposed method is validated with respect to linearity, recovery, limits of detection, and intra-day and inter-day precision.
Challenging Pharmaceutical Analyses by Gas Chromatography with Vacuum Ultraviolet Detection J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-28 Jinjian Zheng, Chunli Huang, Simon Wang
Vacuum ultraviolet (VUV) detector for gas chromatography (GC) provides qualitative spectral information from 125 nm to 240 nm. In this article, this information was applied to facilitate the development of a GC method for challenging pharmaceutical applications. Seven organic solvents were screened for trace level water content using VUV detection at 168 nm, and the results were used to identify n-hexane as a suitable diluent for 4-ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO), a water reactive compound. Selective detection of compounds of interest was demonstrated by varying detection wavelengths. All compounds were detected at 145 nm except for one unknown impurity, which co-eluted with n-hexane solvent. This impurity was detected at 225 nm, where n-hexane has no absorbance. In addition, the VUV spectra were used to: 1) accurately track peaks during early method development; 2) detect co-eluting peaks; 3) match peak identity in a sample vs. a standard; and 4) assess peak purity. With the universal detectability, qualitative spectral information and ease of use, VUV will become a versatile tool for GC for both method development and routine analysis.
Nanoparticle-templated hierarchically porous polymer/zeolitic imidazolate framework as a solid-phase microextraction coatings J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 Milad Ghani, Saeed Masoum, Sayed Mehdi Ghoreishi, Víctor Cerdà, Fernando Maya
A two-step ZnO nanoparticle-directed method has been implemented to prepare polymer monolith/zeolitic imidazolate framework (ZIF) solid-phase microextraction (SPME) fiber coatings with hierarchical micro-meso-macroporosity. The polymer/ZIF monolith was prepared on the surface of a stainless steel wire from a polymerization mixture containing dispersed ZnO nanoparticles. The embedded ZnO nanoparticles in the precursor polymer monolith coating were converted on-fiber to submicrometric porous crystals of the prototypical ZIF-8, based on the coordination of Zn(II) with 2-methylimidazole. The polymer/ZIF monolith coating was applied to the headspace SPME of benzene, toluene, ethylbenzene, and xylenes (BTEX) from water samples, followed by gas chromatography-flame ionization detection (GC-FID).Hierarchically porous polymer/ZIF monolithic coatings showed a superior performance for BTEX extraction in comparison to coatings based on pure macroporous organic polymer monoliths, silicone glue/ZIF-8 coatings, or commercial PDMS coatings. Experimental parameters such as desorption temperature, desorption time, salt concentration, temperature effect, equilibrium time and extraction time were investigated. Under the selected experimental conditions, limits of detection of 0.02–0.11 μg L−1, linear ranges of 0.2–200 μg L−1, relative standard deviations of 4.3–8.2%, and a fiber-to-fiber reproducibility of 8.9–9.8% (n = 3), were obtained. Recoveries higher than 88% were obtained for BTEX analysis in tap water, wastewater and landfill leachates.
Ionic liquid-coated alumina-pretreated micro gas chromatography columns for high-efficient separations J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 Bishnu P. Regmi, Ryan Chan, Arsalan Atta, Masoud Agah
These studies demonstrate the influence of an intermediate layer of aluminum oxide on the separation performance of a room temperature ionic liquid (RTIL)-coated gas chromatography silicon microcolumn. A 1-m long semi-packed column having 190-µm wide and 240-µm deep rectangular cross-sectional channels with embedded arrays of micro pillars was microfabricated. A thin layer of alumina was then deposited on the surface of the channels via atomic layer deposition. Following the alumina deposition, the channels were coated with an RTIL. The separation performance of the RTIL-coated columns with and without the alumina layer was evaluated by measuring the separation efficiency and peak capacity. A substantial increase in separation efficiency was observed in the presence of the alumina layer. The alumina-pretreated columns, at optimum flow rate, exhibited as high as 8,000 plates per meter, which is a 2.1-fold increase as compared to the column with no alumina layer. It is inferred that alumina coating promotes the formation of a more uniform RTIL film, thereby enhancing the separation efficiency. The peak production rates of alumina-RTIL columns for temperature-programmed separation were found to be 0.80 to 1.1 peaks per second, which is an improvement compared to silicon-RTIL columns. The separation performance of these columns were further evaluated by separating a standard 21-component mixture of hazardous organic compounds, a sample of kerosene, diesel, and B20 biodiesel.. These studies open up new possibilities of enhancing the separation efficiency of microcolumns by coating silicon surface with a suitable material prior to depositing an ionic liquid.
Three dimensional characterisation of chromatography bead internal structure using X-ray computed tomography and focused ion beam microscopy J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 T.F. Johnson, J.J. Bailey, F. Iacoviello, J.H. Welsh, P.R. Levison, P.R. Shearing, D.G. Bracewell
X-ray computed tomography (CT) and focused ion beam (FIB) microscopy were used to generate three dimensional representations of chromatography beads for quantitative analysis of important physical characteristics including tortuosity factor. Critical-point dried agarose, cellulose and ceramic beads were examined using both methods before digital reconstruction and geometry based analysis for comparison between techniques and materials examined.X-ray ‘nano’ CT attained a pixel size of 63 nm and 32 nm for respective large field of view and high resolution modes. FIB improved upon this to a 15 nm pixel size for the more rigid ceramic beads but required compromises for the softer agarose and cellulose materials, especially during physical sectioning that was not required for X-ray CT. Digital processing of raw slices was performed using software to produce 3D representations of bead geometry.Porosity, tortuosity factor, surface area to volume ratio and pore diameter were evaluated for each technique and material, with overall averaged simulated tortuosity factors of 1.36, 1.37 and 1.51 for agarose, cellulose and ceramic volumes respectively. Results were compared to existing literature values acquired using established imaging and non-imaging techniques to demonstrate the capability of tomographic approaches used here.
Kinetic performance factor – A measurable metric of separation-time-pressure tradeoff in gas and liquid chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 Leonid M. Blumberg, Gert Desmet
A measurable dimensionless metric of tradeoff between separation, time and pressure in chromatography – the kinetic performance factor (ec) is introduced. Measurable the same way for all LC and GC columns (open-tubular, packed, monolithic, pillar-array, etc., regardless of retention mechanism), ec supersedes metrics of a column structural quality such as dimensionless plate height (h), Bristow-Knox separation impedance (SI), Golay specific performance index (SPI) and others. Peak capacity, and other separation performance measures of a chromatographic system are proportional to ec. To theoretically predict the separation-time performance of a particular column with known ec, two measurable parameters – a column effective diameter (deff) and nominal diffusivity (Dn) were introduced in addition to ec. Quantities ec and Dn represent the properties of column classes while deff represents a particular column. The use of parameters deff, ec and Dn for evaluation of relations between efficiency and void time (tM) in columns of several types has been demonstrated. It is always more time-efficient to use maximum available instrumental pressure (Δpmax) for obtaining a predetermined column efficiency even if that efficiency is relatively low so that operation at Δpmax requires non-optimal flow. It has been also demonstrated that reducing the characteristic cross-sectional dimension (deff, particle size of a packed column, internal diameter of and open-tubular column, etc.) of a column operating at the same Δpmax reduces the column efficiency with the benefit of much larger reduction in the analysis time.
Modelling the enantioresolution capability of cellulose tris(3,5-dichlorophenylcarbamate) stationary phase in reversed phase conditions for neutral and basic chiral compounds ☆ J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 Yolanda Martín-Biosca, Laura Escuder-Gilabert, María José Medina-Hernández, Salvador Sagrado
To the best of our knowledge, the prediction of the enantioresolution ability of polysaccharides-based stationary phases in liquid chromatography for structurally unrelated compounds has not been previously reported. In this study, structural information of neutral and basic compounds is used to model their enantioresolution levels obtained from an immobilised cellulose tris(3,5-dichlorophenylcarbamate) stationary phase in reversed phase conditions. Thirty-four structurally unrelated chiral drugs and pesticides, from seven families, are studied. Categorical enantioresolution levels (RsC, 0 = no baseline enantioresolution and 1 = baseline enantioresolution) are established from the experimental enantioresolution values obtained at a fixed experimental conditions. From 58 initial structural variables, three topological parameters (two of them connected to the chiral carbon), and six molecular descriptors (one of them also related with the chiral carbon), are selected after a discriminant partial least squares refinement process. The molar total charge of the molecule at the working pH is the most important variable. The relationships between RsC and the most important structural variables and the drug/pesticide family are evaluated. An explicit model is proposed to anticipate the RsC levels, which provides 100% of correct anticipations. A criterion is introduced to alert about the compounds that should not be anticipated.
Enantioseparation of fluorinated 3-(aryl)thio-4,4’-bipyridines: insights into chalcogen and π-hole bonds in high-performance liquid chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-25 Paola Peluso, Carlo Gatti, Alessandro Dessì, Roberto Dallocchio, Robin Weiss, Emmanuel Aubert, Patrick Pale, Sergio Cossu, Victor Mamane
A chalcogen bond (ChB) is a σ-hole-based noncovalent interaction between a Lewis base and an electrophilic element of Group VI (O, S, Se, Te), which behaves as a Lewis acid. Recently, we demonstrated that halogen bond, the more familiar σ-hole-based interaction, is able to promote the enantioseparation of chiral compounds in HPLC environment. On this basis, an investigation to detect ChBs, functioning as stereoselective secondary interactions for HPLC enantioseparations, was started off and the results of this study are described herein. Our investigation also focused on the impact of the perfluorinated aromatic ring as a π-hole donor recognition site. For these purposes, seven atropisomeric fluorinated 3-arylthio-4,4’-bipyridines were designed, synthesized and used as potential ChB donors (ChBDs) with two cellulose-based chiral stationary phases (CSPs) containing carbonyl groups as ChB acceptors (ChBAs). In addition, one and two analogues lacking fluorine and sulphur, respectively, were prepared as terms of comparison. The design of the test analytes was computationally guided. In this regard, electrostatic potentials (EPs) associated with σ- and π-holes were computed and the atomic contributions to the sulphur EP maxima were derived using a molecular space partitioning in terms of Bader’s atomic basins. This procedure is akin to the Bader-Gatti electron density source function (SF) decomposition, yet suitably extended to the EP field. For five 3-substituted-4,4’-bipyridines, thermodynamic parameters were derived from van’t Hoff plots. Finally, the use of molecular dynamic (MD) simulation to model ChB in cellulose-analyte complexes was explored. Evidences that σ-hole and π-hole interactions can jointly drive HPLC enantioseparations through recognition sites generated by electronic charge depletion emerged from both experimental results and theoretical data.
Separation and Identification of Polymeric Dispersants in Detergents by Two-Dimensional Liquid Chromatography J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-26 Peilin Yang, Wei Gao, Jan E. Shulman, Yunshen Chen
Polymeric dispersants are an important ingredient in many consumer products. Their separations and identifications in final product formulation can be very challenging due to the presence of multiple polymeric dispersants at different levels and the presence of other polymeric and small-molecule components. In this study, using nearly comprehensive two-dimensional liquid chromatography (2D-LC), various water-soluble polymer and co-polymer dispersants were separated with aqueous size exclusion chromatography (SEC) in the first dimension (1D) and gradient elution reversed-phase liquid chromatography (RPLC) in the second dimension (2D). Detection of the polymeric dispersants was accomplished by evaporative light scattering detector (ELSD). A large ID (8.0 mm) SEC column used in common one-dimensional SEC practices was directly adopted in the 2D setup for rapid method development. A close representation of fully comprehensive 2D separation was achieved even with 60% of 1D eluent diverted to waste, demonstrating the flexibility and versatility of having SEC in 1D for two dimensional separation of polymers. Important method parameters, such as 2D column dimensions and flow rate, gradient conditions, and buffer pH were studied. Practical aspects of routine industrial applications such as solvent consumption and analysis time were also considered. This method was exploited for quick identification of polymeric dispersants in commercial detergent samples. Nine detergent samples were screened and polymeric dispersants and additional polymer features were detected in the samples.
Matrix solid-phase dispersion associated to gas chromatography for the assessment in honey bee of a group of pesticides of concern in the apicultural field J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-26 Arantza Balsebre, María E. Báez, Jessica Martínez, Edwar Fuentes
A method based on matrix solid-phase dispersion (MSPD) associated to gas chromatography-flame photometric detection (GC-FPD), GC-electron capture detection (GC-ECD) and GC-mass spectrometry (GC-MS) for confirmation purposes, was developed for the determination of a representative group of twelve pesticides in honeybee with particular concern in the apicultural field (fipronil, thiamethoxam, acetamiprid, acrinathrin, metamidophos, dimetoathe, diazinon, chlorpyrifos, methidathion, profenophos, azinphos methyl and coumaphos). Factors influencing the extraction efficiency of MSPD were investigated and optimized through response surface method. The use of octadecylsilyl (C18) sorbent combined with a florisil clean-up and acetonitrile-methanol (99:1) elution was the optimal condition for the extraction of the selected pesticides. Under this condition the recovery of pesticides at the limit of quantification of the method (0.007 to 0.050 µg g -1) ranged from 68 to 102% with RSDs for within-laboratory reproducibility ≤ 20%. The proposed method was applied to the analysis of honeybees collected in 68 field hives from areas of great apicultural and agricultural development in central Chile. In 65% of these samples eight different pesticides were detected. Pesticides most frequently found were chlorpyrifos (34% of the samples, <0.017-0.067 μg g-1), acrinathrin (32% of the samples, <0.020-0.026 μg g-1) and diazinon (10% of the samples at values <0.015 μg g-1). The incidence of these pesticides in bees can be related to their high employ in central Chile, use to combat the varroosis in hives and hydrophobicity.
Profiling of N-linked glycans from 100 cells by capillary electrophoresis with large-volume dual preconcentration by isotachophoresis and stacking J. Chromatogr. A (IF 3.716) Pub Date : 2018-06-23 Takayuki Kawai, Nobutoshi Ota, Akiko Imasato, Yoko Shirasaki, Koji Otsuka, Yo Tanaka
Glycan structure is changed in response with pathogenesis like cancer. Profiling of glycans from limited number of pathogenetic cells in an early-stage tissue is essential for discovering effective drugs. For analyzing tiny biological samples, we developed sensitive, high-resolution, and salt-tolerant method for analyzing trace level of N-linked glycans by coupling capillary electrophoresis (CE), laser-induced fluorescence (LIF) detection, and a new online sample preconcentration (OSP) method named “large-volume dual preconcentration by isotachophoresis and stacking (LDIS)”, which is composed of two OSP methods, large-volume sample stacking (LVSS) and transient isotachophoresis (tITP). A typical LDIS-CE-LIF protocol was simple: a short-plug of leading electrolyte (LE) and large-volume sample solution were introduced to a capillary, followed by application of constant voltage. In the analysis of glucose ladder labeled with 8-aminopyrene-1,3,6-trisulfonic acid with 10 mM sodium chloride as LE, up to 2300-fold sensitivity increase was achieved with higher resolution than those in normal CE. By applying pressure assist during preconcentration, both viscous gel electrolyte and salty matrix of up to 10 mM NaCl were acceptable. Finally, N-glycans from approximately 100 cells (HeLa, MCF7, and HepG2) were analyzed as the model of localized tumor cells. From 30 to 40 glycans were successfully detected with almost same profile of large-scale sample. N-glycan structure could be predicted by searching glucose-unit value via Glycobase database, indicating that HepG2 expressed more sialylated glycans and MCF-7 expressed less glycans respectively, comparing with HeLa cells. It suggests the potential of LDIS-CE-LIF for discovery of disease-specific N-linked glycans in microscale environment.
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