Chitosan-based molecular imprinted polymer for extraction and spectrophotometric determination of ketorolac in human plasma

doi:10.1016/j.saa.2020.118668

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy

Volume 241, 5 November 2020, 118668

https://doi.org/10.1016/j.saa.2020.118668 Get rights and content

Highlights

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SPE of ketorolac was successfully performed in aqueous solutions and plasma samples.
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Chitosan-based MIP enabled selective spectrophotometric determination of ketorolac.
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Chitosan-based MIP was prepared by sol-gel method; characterized using SEM and FTIR.
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The spectrophotometric method was validated according to the ICH M10 guidelines.

Abstract

A selective chitosan-based ion exchange molecular imprinted polymer (MIP) was prepared for ketorolac (KET) using the sol-gel method and glutaraldehyde as a crosslinker. The nonimprinted polymer (NIP) was prepared and used as a control, during the whole experiment. The chemical and morphological characteristics of the prepared polymers were investigated using FTIR and SEM, respectively. The prepared MIP was applied to determine the optimum operational conditions for KET extraction from dilute aqueous solutions. The adsorption step was performed at pH 5 and a contact time of 20 min, using 0.1 N HCl as an elution solvent for 30 min. The specificity of the prepared polymer was indicated by an imprinting factor of 1.45. The prepared MIP was successfully applied for selective solid phase extraction and subsequent determination of KET in spiked human plasma samples over a range of 2–20 μg/mL, with a mean % recovery of 94.62% using derivative spectroscopy.

Graphical abstract

Introduction

The quantitative determination of drugs in complex biological matrices e.g. plasma requires a treatment step prior to instrumental analysis to reduce the consequences of the residual matrix build up in the analytical system, which may affect the results and the instruments [1,2]. Among the different pretreatment approaches, solid phase extraction (SPE) is considered one of the most popular techniques applied for cleanup and preconcentration and trace analysis of biological [[3], [4], [5]] and environmetal samples [6,7]. Compared with other sample preparation techniques, SPE is more selective than protein precipitation, more efficient than liquid-liquid extraction and can be operated in both batch and automated processes. However, the lack of selectivity is still considered the main drawback of conventional SPE sorbents, resulting in co-extraction of interfering components with the target analytes [8]. Several trials to increase the selectivity of the SPE sorbent were attempted. Recently, molecular imprinted polymers (MIPs) have been used as sorbents in SPE from various kinds of matrices [5,9] in addition to other fields such as catalysis [10], chromatographic separation [11], and sensors [12] due to their outstanding merits such as selectivity, physical and thermal stability as well as low cost and ease of preparation. MIPs are synthetic polymers possessing specific cavities designed to a target molecule; known as a template. In the imprinting process, monomers form a complex with the template through covalent or non-covalent interaction before crosslinking. After removing the template molecules, complementary cavities to the template molecules in size, shape, and functional groups are left behind, which consequently allows their selective uptake [13]. MIPs can be considered synthetic alternatives to immunosorbents, due to their high affinity and selectivity for a specific target or group of structurally related analytes [14]. Unlike immunosorbents, MIPs can be easily and reproducibly prepared, used under harsh conditions (high temperatures, non-aqueous and extreme pH conditions), regenerated, and reused with little loss of performance. Compared to the general purpose sorbents that are commonly used in SPE, such as bonded silica (C8, C18, CN), styrene-divinyl benzene copolymers (PS-DVB) and graphitized carbon black (GCB), MIPs are analyte specific sorbents, possessing tailor-made recognition sites, that can specifically rebind to a target molecule in preference to analogous compounds [15,16]. Wide varieties of monomers have been used in the preparation of MIPs among which, polysaccharides are considered a promising class of green monomers, recently applied for the preparation of water compatible MIPs [17,18].

Chitosan is obtained by deacetylation of chitin, the most abundant naturally occurring amino polysaccharide, possess several advantages such as non-toxicity, bioavailability, and biocompatibility [19]. The protonation of the amino groups of chitosan and its composite at low pH facilitates the adsorption of heavy metal ions, dyes, and protein molecules via various interaction mechanisms such as metal chelation (via co-ordinate covalent bond), electrostatic or ionic interaction (with the protonated C₂-NH₂), and hydrogen bonding (with C₃- and C₆-OH moiety) [20]. However, an additional crosslinking reaction is required to enhance its stability and increase the feasibility of its application [17]. Among several crosslinkers, glutaraldehyde is considered one of the most commonly used reactive reagents. It reacts either with the hydroxyl group forming acetal or the amino group forming imine (Schiff's base) [17]. Glutaraldehyde crosslinked chitosan has been utilized in the preparation of ion exchange resin for selective removal of metal ions from water [21]. In addition, a chitosan/glutaraldehyde MIP for enantioselective separation of L-glutamic acid was reported [22]. However, limited few work deals with the application of chitosan ion exchange MIPs in drug analysis.

KET is a weakly acidic arylalkanoic acid derivative NSAID, used for pain treatment [23]. The pharmacokinetic determination of KET is limited to chromatographic methods coupled with LLE [[24], [25], [26]], conventional SPE [27,28] or protein precipitation [29]. Despite of their good analytical results, chromatographic methods are expensive and time consuming, compared with the spectrophotometric methods. UV spectroscopy is a fast, reliable, relatively cheap, and simple to operate, however it is not suited for the determination of KET in plasma mainly due to the matrix effect [30]. The use of selective SPE enables the sample cleanup, decreases the coexisting interfering matrix components [31] and pre-concentrate the sample.

The present work aimed to prepare a green operated KET specific chitosan-based ion exchange MIP sorbent whose specificity to be utilized for sample cleanup to enable KET determination in spiked plasma using derivative spectrophotometry. To the best of our knowledge, this is the first report for spectrophotometric determination of a drug in plasma using a chitosan-based MIP.

Section snippets

Materials

Chitosan (medium molecular weight, deacetylation degree 75–85%) was purchased from Sigma-Aldrich (www.sigmaaldrich.com, Missouri, USA). Ketorolac tromethamine (KET) (99.99%) was supplied by Pharco Pharmaceuticals (www.pharco.org, Alexandria, Egypt). Ibuprofen, ketoprofen, naproxen, diclofenac, and tolmetin were kindly supplied by Sigmatec for Pharmaceutical Industries (Giza, Egypt). Glutaraldehyde (GLA) (50%, analytical grade) was purchased from ADWIC (www.elnasrpharma.com, Qaliubiya, Egypt). KH

Preparation of KET imprinted and nonimprinted crosslinked chitosan

KET is an acidic drug with a pK_a of 3.50 due to the aliphatic carboxylic acid. Therefore, at pH values above 3.50, KET is ionized and its net charge is negative. On the other hand, chitosan is considered as cationic polysaccharide with pK_a values varying between 6.17 and 6.51 depending on the molecular weight and the deacetylation degree [34]. Therefore, at pH below 6.00, the net charge of chitosan is positive. The utilization of ionic interactions between chitosan and acidic drugs as

Conclusion

Chitosan, a green alternative for the commonly used acrylate derivatives and other non-ecofriendly monomers, was used for the preparation KET selective ion exchange MIP. A chitosan-based ion exchange MIP was successfully synthesized and used as a specific sorbent for dispersive SPE of KET prior to its spectrophotometric determination. The NIP was prepared without template and used as a control throughout the whole experiments. The selectivity of the prepared polymer was confirmed by the

CRediT authorship contribution statement

Mokhtar Mabrouk: Conceptualization, Formal analysis, Writing - review & editing. Sherin F. Hammad: Conceptualization, Formal analysis, Writing - review & editing. Aya A. Abdella: Investigation, Conceptualization, Formal analysis, Writing - original draft. Fotouh R. Mansour: Conceptualization, Formal analysis, Writing - original draft, Writing - review & editing.

Declaration of competing interest

The authors declare that they have no competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Chitosan-based molecular imprinted polymer for extraction and spectrophotometric determination of ketorolac in human plasma

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Materials

Preparation of KET imprinted and nonimprinted crosslinked chitosan

Conclusion

CRediT authorship contribution statement

Declaration of competing interest

J. Chromatogr. B

J. Chromatogr. A

TrAC Trends Anal. Chem.

Int. J. Electrochem. Sci.

TrAC Trends Anal. Chem.

TrAC Trends Anal. Chem.

J. Hazard. Mater.

Int. J. Biol. Macromol.

J. Chromatogr. B Biomed. Sci. Appl.

J. Chromatogr. B Biomed. Sci. Appl.

J. Young Pharm.

Talanta.

Sensors Actuators B Chem.

Materials (Basel)

Eur. J. Pharm. Biopharm.

Colloids Surf. B

Carbohydr. Polym.

Acta Pharm. Sin. B

Bull. Fac. Pharm. Cairo Univ.

Biological sample preparation: attempts on productivity increasing in bioanalysis

Bioanalysis.

Past, present, and future of solid phase extraction: a review

Crit. Rev. Anal. Chem.

The sample matrix and its influence on method development

Magnetic nanoparticle based dispersive micro-solid-phase extraction for the determination of malachite green in water samples: optimized experimental design

New J. Chem.

Separation and enrichment of chromium, copper, nickel and lead in surface seawater samples on a column filled with amberlite xad-2000

Anal. Lett.

Solid-phase extraction in clinical biochemistry

Ann. Clin. Biochem.