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Collision energy-breakdown curves – An additional tool to characterize MS/MS methods Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-10-20 Sophie Mörlein; Carina Schuster; Michael Paal; Michael Vogeser
Background In tandem mass spectrometry, analyte detection is based on collision-induced fragmentation, which is modulated by the collision energy (CE) setting. Variation in CE leads to differential ion yield, and optimization is usually performed empirically as “tuning” during method development. Our aim was to build a method to objectify the impact of collision energy settings on ion yield for individual
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Development and validation of a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of phthalates and bisphenol a in serum, urine and follicular fluid Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-10-28 Anna Pia Dima; Lucia De Santis; Cristina Verlengia; Francesco Lombardo; Andrea Lenzi; Monica Mazzarino; Francesco Botrè; Donatella Paoli
Phthalates and bisphenol A interfere with the synthesis, secretion, transport, binding, metabolism, and excretion of endogenous hormones and, for this reason, are classified as endocrine disruptors. We are here presenting an analytical method for the simultaneous detection of six phthalates metabolites and bisphenol A in different biological fluids (urine, serum and follifular fluid) by liquid chromatography
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Analysis of urinary VOCs using mass spectrometric methods to diagnose cancer: A review Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-10-31 Bruno Ruiz Brandão da Costa; Bruno Spinosa De Martinis
The development of non-invasive screening techniques for early cancer detection is one of the greatest scientific challenges of the 21st century. One promising emerging method is the analysis of volatile organic compounds (VOCs). VOCs are low molecular weight substances generated as final products of cellular metabolism and emitted through a variety of biological matrices, such as breath, blood, saliva
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Analysis of 17 fentanyls in plasma and blood by UPLC-MS/MS with interpretation of findings in surgical and postmortem casework Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-10-28 Jonathan P. Danaceau; Michelle Wood; Melissa Ehlers; Thomas G. Rosano
The opioid crisis is linked to an increased misuse of fentanyl as well as fentanyl analogs that originate from the illicit drug market. Much of our current understanding of fentanyl and fentanyl analog use in our communities comes from postmortem toxicology findings. In the clinical settings of addiction medicine and pain management, where the opioid abuse potential is high, the use of fentanyl, as
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A proposal for score assignment to characterize biological processes from mass spectral analysis of serum Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-09-09 Joanna Roder; Lelia Net; Carlos Oliveira; Krista Meyer; Senait Asmellash; Sabine Kasimir-Bauer; Harvey Pass; Jeffrey Weber; Heinrich Roder; Julia Grigorieva
Introduction Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient’s disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help
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Mass spectrometry in clinical glycomics: The path from biomarker identification to clinical implementation Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-08-27 N. de Haan; M. Wuhrer; L.R. Ruhaak
Over the past decades, the genome and proteome have been widely explored for biomarker discovery and personalized medicine. However, there is still a large need for improved diagnostics and stratification strategies for a wide range of diseases. Post-translational modification of proteins by glycosylation affects protein structure and function, and glycosylation has been implicated in many prevalent
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Direct detection of intact Klebsiella pneumoniae carbapenemase variants from cell lysates: Identification, characterization and clinical implications Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-07-18 William M. McGee, Matthew L. Faron, Jason R. Neil, Scott R. Kronewitter, Blake W. Buchan, Nathan A. Ledeboer, James L. Stephenson
Introduction Carbapenemase-producing organisms (CPOs) are a growing threat to human health. Among the enzymes conferring antibiotic resistance produced by these organisms, Klebsiella pneumoniae carbapenemase (KPC) is considered to be a growing global health threat. Reliable and specific detection of this antibiotic resistance-causing enzyme is critical both for effective therapy and to mitigate further
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Development of dried blood spot quality control materials for adenosine deaminase severe combined immunodeficiency and an LC-MS/MS method for their characterization Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-07-10 Brian Young, Jessica Hendricks, David Foreman, C. Austin Pickens, Candice Hovell, Víctor R. De Jesús, Christopher Haynes, Konstantinos Petritis
Adenosine deaminase severe combined immunodeficiency (ADA-SCID) is an autosomal recessive disorder in which a lack of ADA enzyme prevents the maturation of T- and B-cells; early intervention is crucial for restoring immune function in affected neonates. ADA is responsible for purine metabolism and—in its absence—adenosine, deoxyadenosine, and S-adenosylhomocysteine build up and can be detected in the
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Averaging of results derived from different, simultaneously acquired mass transitions in ID-LC-MS/MS – Potential impact on measurement imprecision Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-06-04 Carina Schuster, Katharina Habler, Michael Vogeser
Background LC–MS/MS allows for many measurands monitoring different mass transitions simultaneously. So far, such alternative mass transitions are usually assessed as “quantifier and qualifier ions” in order to rule out interferences in individual samples. However, quantification can also be based on assessment of alternative mass transitions for both the measurand and its internal standard, with two
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Determination of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis by MALDI-TOF MS in clinical isolates from Latvia Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-03-26 Laura Alksne, Svetlana Makarova, Jeļena Avsejenko, Alla Cibrovska, Julija Trofimova, Olga Valciņa
Rapid identification of methicillin-resistant Staphylococcus could ensure appropriate medical care. A total of 409 Staphylococcus spp. strains were used to develop a reliable MALDI-TOF method for species identification. We tested twelve S. aureus strains to compare three different sample preparation methods and the reproducibility of the methicillin-resistant m/z 2414 ± 2 indicator peak with direct
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Quantification of volatile metabolites in exhaled breath by selected ion flow tube mass spectrometry, SIFT-MS Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-02-13 Patrik Španěl, David Smith
Selected ion flow tube mass spectrometry, SIFT-MS, is a non-separative method for direct quantitative analyses of volatile compounds, VOCs, in air and humid breath based on chemical ionization. Selected reagent ions, either H3O+, NO+ or O2+ (non-reactive with major components of air), ionize analyte molecules during a defined time in a flow tube by ion-molecule reactions thus producing analyte ions
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An isotope dilution LC–MS/MS-based candidate reference method for the quantification of androstenedione in human serum and plasma Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-01-23 Katrin Gradl, Judith Taibon, Neeraj Singh, Eva Albrecht, Andrea Geistanger, Stephan Pongratz, Stefan Hutzler, Magdalena Mayer, Christine Kleinschmidt, Christian Geletneky, Verena Hofmann, Daniel Köppl, Manfred Rauh, Uwe Kobold
The accurate measurement of androstenedione in human serum and plasma is required for steroid profiling to assure the appropriate diagnosis and differential diagnosis of hyperandrogenism. In this work, we introduce an isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS) candidate reference measurement procedure for the quantification of androstenedione in human serum and plasma
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Assessing a method and reference material for quantification of vitamin D binding protein during pregnancy Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-01-23 Lisa E. Kilpatrick, Ashley S.P. Boggs, W. Clay Davis, Stephen E. Long, James H. Yen, Karen W. Phinney
Vitamin D plays a vital role in successful pregnancy outcomes for both the mother and fetus. Vitamin D is bound to vitamin D binding protein (VDBP) in blood and is carried to the liver, kidneys and other target tissues. Accurate measurements of the clinically measured metabolite of vitamin D, 25-hydroxyvitamin D [25(OH)D], depend on complete removal from the binding protein. It has been found that
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More sensitivity is always better: Measuring sub-clinical levels of serum thyroglobulin on a µLC–MS/MS system Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-01-14 Christopher M. Shuford, Jay S. Johnson, J. Will Thompson, Patricia L. Holland, Andrew N. Hoofnagle, Russell P. Grant
Although liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays for thyroglobulin (Tg) are resistant to autoantibody (TgAb) interference, recent studies have demonstrated approximately 40% of TgAb-positive individuals with recurrent thyroid cancer have Tg concentrations below the lower limit of quantification (LLOQ) of the LC–MS/MS assays described to date (i.e., <0.5 ng/mL), resulting in
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Role of mass spectrometry in establishing safety and efficacy of botanical dietary supplements Clin. Mass Spectrom. (IF 1.172) Pub Date : 2020-01-07 Richard B. van Breemen
As in drug discovery and development, mass spectrometry has become essential at all stages for establishing the safety and efficacy of botanical dietary supplements. Applications of mass spectrometry to the development of botanical dietary supplements include preclinical studies of the mechanisms of action (e.g., proteomic target identification and validation); identification of active natural products
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Measurement of 2-hydroxyglutarate enantiomers in serum by chiral gas chromatography-tandem mass spectrometry and its application as a biomarker for IDH mutant gliomas Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-11-21 Shinji K. Strain, Morris D. Groves, Kelly L. Olino, Mark R. Emmett
(R)-2-hydroxyglutarate (R-2-hg) is a metabolite produced under physiologic conditions but also by tumors harboring isocitrate dehydrogenase (IDH) mutations. Detection is challenging as it must be distinguished from its enantiomer (S)-2-hydroxyglutarate (S-2-hg), which is also produced in the body but can increase under hypoxic conditions. A chiral gas chromatography-tandem mass spectrometry (GC–MS/MS)
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Medical mass spectrometrist (MMS) training and certification: A key step to expanding routine clinical mass spectrometry usage in Japan Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-11-13 Fumio Nomura, Toyofumi Nakanishi, Kazuo Igarashi, Seiji Yamaguchi, Mitsutoshi Setou, Toshimitsu Niwa
Mass spectrometry (MS) is increasingly used in clinical medicine in Japan. In contrast to the successful application of MS in clinical microbiology, the adoption of MS-based assays for routine testing in clinical chemistry is very slow. In order to promote the significant benefits that MS platforms bring to laboratory medicine and patient care, the Japanese Society for Biomedical Mass Spectrometry
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Development and validation of a liquid chromatography-tandem mass spectrometry method for determination of ibuprofen in human plasma Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-10-25 Apichaya Puangpetch, Anchalee Limrungsikul, Santirhat Prommas, Pattarawit Rukthong, Chonlaphat Sukasem
Ibuprofen is widely used to reduce fever, pain, and inflammation and in the treatment of patent ductus arteriosus (PDA) in preterm infants. However, to study the impact of pharmacokinetics of ibuprofen on the rate of ductus arteriosus closure in humans, a quantitative method is required. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a highly sensitive, accurate, reliable, fast, and simple
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Development of a LC-MS/MS method for urinary hydroxytyrosol as a marker for consumption of olive oil Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-10-16 Lisa M. Johnson, Anthony A. Killeen, Jesse C. Seegmiller
The aim of this study was to develop and validate a LC-MS/MS method to quantitate hydroxytyrosol in urine for clinical studies to monitor compliance of consumption of dietary extra virgin olive oil. Both pre-analytical and analytical issues were examined. The stability of hydroxytyrosol was monitored in both urine and synthetic urine at four different temperatures (room temperature, 4 °C, −20 °C, or
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Application of protein set enrichment analysis to correlation of protein functional sets with mass spectral features and multivariate proteomic tests Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-09-13 Julia Grigorieva, Senait Asmellash, Carlos Oliveira, Heinrich Roder, Lelia Net, Joanna Roder
Mass spectral data from multiple samples are suitable for a hypothesis-free development of clinically useful multivariate tests using modern machine learning techniques. However, the transition from discovery to adoption of proteomic tests has proved challenging. Slow adoption of these tests in clinical practice is, in part, related to insufficient understanding of the biological mechanisms underlying
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Tandem mass spectrometry in the clinical laboratory: A tutorial overview Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-09-06 J. Grace van der Gugten
Tandem mass spectrometry (tandem MS) is a powerful technique that directly measures compounds based on their molecular weight. Liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), a type of tandem MS, has been increasingly adopted by clinical laboratories in recent years. While it is complicated and challenging, it has selectivity and accuracy advantages over more traditional laboratory
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Determining histone H4 acetylation patterns in human peripheral blood mononuclear cells using mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-08-10 Esther Marie Bux, Victor Solis-Mezarino, Christoph Kuhm, Bernd H. Northoff, Ivan Karin, Thomas Klopstock, Lesca M. Holdt, Moritz Völker-Albert, Axel Imhof, Shahaf Peleg
Misregulated chromatin remodeling via erroneous histone acetylation has been linked with multiple diseases including many age-associated maladies. Previous studies on histone acetylation have utilized specific histone acetylation antibodies as a primary quantification tool. However, antibodies that target specific histone modifications frequently lack sufficient sensitivity and specificity, making
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Detection and characterization of TDP-43 in human cells and tissues by multiple reaction monitoring mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-07-19 Taylor D. Pobran, Lauren M. Forgrave, Yu Zi Zheng, John G.K. Lim, Ian R.A. Mackenzie, Mari L. DeMarco
Transactive response DNA-binding protein 43 kDa (TDP-43) is a highly conserved and widely expressed protein in human tissues that regulates nucleic acid processing. In frontotemporal dementia and amyotrophic lateral sclerosis, however, TDP-43 forms insoluble aggregates in central nervous tissues. These pathological deposits of TDP-43 have been primarily studied by ligand binding, namely western blot
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A simplified and sensitive immunoprecipitation mass spectrometry protocol for the analysis of amyloid-beta peptides in brain tissue Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-07-19 B.C. Richard, T.A. Bayer, S. Bergström Lind, G. Shevchenko, J. Bergquist
In the field of Alzheimer’s disease, there is an urgent need for novel analytical tools to identify disease-specific biomarkers and to evaluate therapeutics. Preclinical trials commonly employ amyloid beta (Aβ) peptide signatures as a read-out. In this paper, we report a simplified and detailed protocol for robust immunoprecipitation of Aβ in brain tissue prior to mass spectrometric detection exemplified
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Use of the tau protein-to-peptide ratio in CSF to improve diagnostic classification of Alzheimer’s disease Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-07-15 Karl Hansson, Rahil Dahlén, Oskar Hansson, Elin Pernevik, Ross Paterson, Jonathan M. Schott, Nadia Magdalinou, Henrik Zetterberg, Kaj Blennow, Johan Gobom
Cerebrospinal fluid (CSF) tau and phospho-tau are well established biomarkers of Alzheimer’s disease. While these measures are conventionally referred to as ‘total tau’ (T-tau) and ‘phospho-tau’ (P-tau), several truncated and modified tau forms exist that may relay additional diagnostic information. We evaluated the diagnostic performance of an endogenous tau peptide in CSF, tau 175–190, in the phosphorylated
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Identification of potential endometriosis biomarkers in peritoneal fluid and blood plasma via shotgun lipidomics Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-05-31 Natalia Starodubtseva, Vitaliy Chagovets, Anna Borisova, Dinara Salimova, Natalia Aleksandrova, Konstantin Chingin, Huanwen Chen, Vladimir Frankevich
Endometriosis is a recurrent and benign gynecological disorder, defined by the ectopic presence of endometrium. About 10% of reproductive-aged women suffer from endometriosis. There are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis today. Here, we present our efforts to determine the diagnostic accuracy of biomarkers in peritoneal fluid
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A brief update on mass spectrometry applications to routine clinical endocrinology Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-05-29 Daniel T. Holmes
Mass spectrometry in clinical laboratories has traditionally focussed on small molecule analysis making endocrinology applications a natural choice given the numerous diagnostic targets in the steroid family, many of which could be multiplexed. Over time, methods for lower abundance steroids were successfully translated meaning that almost all small molecule targets in clinical endocrinology could
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Development of a CDC-certified total testosterone assay for adult and pediatric samples using LC–MS/MS Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-05-27 Michal Star-Weinstock, Subhakar Dey
Background Highly accurate and sensitive method to measure testosterone in hypogonadal male, female and children is vital for proper diagnosis of hormone-related conditions and their treatment. Objective To develop an accurate and robust total testosterone ESI-LC-MS/MS quantification method with a simple sample preparation workflow and sufficient sensitivity for serum or plasma samples of all gender
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A semi-automated, isotope-dilution high-resolution mass spectrometry assay for therapeutic drug monitoring of antidepressants Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-05-21 Johanna M. Lindner, Michael Vogeser, Katharina Sorg, Stefanie H. Grimm
Background Therapeutic drug monitoring (TDM) of antidepressants is important to ensure compliance and to rule out pharmacokinetic abnormalities. Therefore, reliable methods for quantification are important for clinical laboratories. Most of the currently used mass spectrometry methods use triple quadrupoles as mass analyzers. We aimed to develop a method using high-resolution mass spectrometry (HRMS)
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Data analysis of MS-based clinical lipidomics studies with crossover design: A tutorial mini-review of statistical methods Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-05-20 Xueheng Zhao, Liang Niu, Carlo Clerici, Roberta Russo, Melissa Byrd, Kenneth D.R. Setchell
Clinical lipidomics using mass spectrometry (MS) is important to support discovery of biomarkers for diagnosis and understanding the pathophysiology of diseases. Frequently, lipidomics data from clinical studies have large variations among individuals because the human metabolome/lipidome is strongly influenced by genotype, daily activity, diet and gut flora. This inter-personal variability makes data
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Compliance testing of patients in ADHD treatment with lisdexamphetamine (Elvanse®) using oral fluid as specimen Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-04-22 Michael Böttcher, David Kühne, Olof Beck
Pharmacological treatment of the attention-deficit/hyperactivity disorder (ADHD) includes use of the psychostimulant amphetamine. Non-adherence to medication is a well-documented problem in ADHD treatment and a cause of treatment failure. The study evaluated the possibility of using oral fluid for compliance monitoring during treatment with lisdexamphetamine (Elvanse®). UPLC-MS/MS methods for general
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The Importance of Clinical Tissue Imaging. Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-04-19 Jeffrey M Spraggins,Kristina Schwamborn,Ron M A Heeren,Livia S Eberlin
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Unified representation of high- and low-resolution spectra to facilitate application of mass spectrometric techniques in clinical practice Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-03-25 E.S. Zhvansky, A.A. Sorokin, S.I. Pekov, M.I. Indeykina, D.G. Ivanov, V.A. Shurkhay, V.A. Eliferov, D.S. Zavorotnyuk, N.G. Levin, K.V. Bocharov, S.I. Tkachenko, M.S. Belenikin, A.A. Potapov, E.N. Nikolaev, I.A. Popov
The majority of research in the biomedical sciences is carried out with the highest resolution accessible to the scientist, but, in the clinic, cost constraints necessitate the use of low-resolution devices. Here, we compare high- and low-resolution direct mass spectrometry profiling data and propose a simple pre-processing technique that makes high-resolution data suitable for the development of classification
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A sensitive method for the simultaneous UHPLC-MS/MS analysis of milrinone and dobutamine in blood plasma using NH4F as the eluent additive and ascorbic acid as a stabilizer Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-03-18 Kalev Takkis, Rūta Veigure, Tuuli Metsvaht, Maarja Hallik, Mari-Liis Ilmoja, Joel Starkopf, Karin Kipper
The purpose of this work was to develop and validate an HPLC-MS/MS method suitable for quantifying two important cardiovascular drugs, milrinone and dobutamine, in neonatal and paediatric patients’ blood plasma samples. Sufficiently low LLOQ levels were required to obtain adequate pharmacokinetic data for the evaluation of optimal dosing. Since the specifics of the patient group set some restrictions
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Mass spectrometric quantification of plasma glycosphingolipids in human GM3 ganglioside deficiency Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-03-16 Kazuhiro Aoki, Adam D. Heaps, Kevin A. Strauss, Michael Tiemeyer
Background Among Amish communities of North America, biallelic mutations of ST3GAL5 (c.694C > T) eliminate synthesis of GM3 and its derivative downstream a- and b-series gangliosides. Systemic ganglioside deficiency is associated with infantile onset psychomotor retardation, slow brain growth, intractable epilepsy, deafness, and cortical visual impairment. We developed a robust quantitative assay to
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Rapid method towards proteomic analysis of dried blood spots by MALDI mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-03-15 Grace M. Samenuk, Andrea R. Kelley, George Perry, Stephan B.H. Bach
Neonatal dried blood spots (DBS) are routinely utilized in the clinical setting as a diagnostic tool for various genetic disorders and infectious diseases. DBS allow for minimally invasive, small volume blood collection and are stored at room temperature. Neonatal whole blood and serum samples can be important in determining genetic risk factors and predicting infantile disease; however, at the present
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Diagnosis and the importance of early treatment of tyrosinemia type 1: A case report Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-02-02 Ana Škaričić, Marija Zekušić, Ksenija Fumić, Dunja Rogić, Valentina Uroić, Danijela Petković Ramadža, Tamara Žigman, Ivo Barić
Tyrosinemia type 1 is an autosomal recessive aminoacidopathy caused by fumarylacetoacetate hydrolase (FAH) deficiency. Consequently, tyrosine and its metabolites accumulate, resulting in liver and kidney toxicity. Symptoms of the disease usually manifest after three weeks of life and include vomiting, failure to thrive, hepatomegaly, jaundice, bleeding diathesis, rickets and renal tubular dysfunction
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Development and evaluation of matrix application techniques for high throughput mass spectrometry imaging of tissues in the clinic Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-01-28 Lennart R.S. Huizing, Shane R. Ellis, Bart W.A.M.M. Beulen, Florian P.Y. Barré, Paul B. Kwant, Rob J. Vreeken, Ron M.A. Heeren
Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a sensitive label-free technique that can be used to study a wide variety of clinical phenotypes. In this context, MSI offers huge diagnostic potential by supporting decision making in the determination of personalized treatment strategies. However, improvements in throughput and robustness are still needed before
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An automated mass spectrometric blood test for therapeutic drug monitoring of infliximab Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-01-28 J. Grace van der Gugten, Brian Bressler, Mari L. DeMarco
Infliximab is a monoclonal antibody therapy used to treat several chronic immune-mediated diseases, including Crohn’s disease, ulcerative colitis, and rheumatoid arthritis. Infliximab acts by binding to tumor necrosis factor and, thus, inhibiting the inflammatory cascade. While it is a highly effective therapy, a subset of patients on infliximab will develop a loss of response to therapy. In these
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Detection of in utero Exposure to Cannabis in Paired Umbilical Cord Tissue and Meconium by Liquid Chromatography-Tandem Mass Spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-01-24 Triniti L. Jensen, Fang Wu, Gwendolyn A. McMillin
Understanding levels of in utero drug exposure is important to properly customize the immediate, as well as ongoing, medical and social management needs of affected newborns. Here, we present the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of 4 cannabinoid analytes in two neonatal matrices. The analytes targeted were Δ9-tetrahydrocannabinal
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Simultaneous measurement of 18 steroids in human and mouse serum by liquid chromatography–mass spectrometry without derivatization to profile the classical and alternate pathways of androgen synthesis and metabolism Clin. Mass Spectrom. (IF 1.172) Pub Date : 2019-01-06 Reena Desai, D. Tim Harwood, David J. Handelsman
Background The recently identified alternate, or backdoor, pathway of DHT synthesis provides important novel information on androgen biosynthesis beyond the classical pathway. We report a rapid and versatile liquid chromatography–tandem mass spectrometry (LC–MS/MS) method to simultaneously and accurately quantify key steroids in human or mouse serum involved in either the classical or backdoor androgen
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Long-term stability of the alcohol consumption biomarker phosphatidylethanol in erythrocytes at −80 °C Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-12-28 Hans-Åke Lakso, Anna Wuolikainen, Anneli Sundkvist, Ingegerd Johansson, Stefan L. Marklund
Phosphatidylethanol (PEth) is a recently introduced biomarker with high specificity, high sensitivity, and response correlating with alcohol consumption. It has the potential to be a valuable biomarker in population studies on the health effects of alcohol, however its stability in long-term stored blood is not known. We used LC-MS/MS to assess the stability of PEth-16:0/18:1 in blood samples (packed
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Clinically-relevant Shiga toxin 2 subtypes from environmental Shiga toxin-producing Escherichia coli identified by top-down/middle-down proteomics and DNA sequencing Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-12-05 Clifton K. Fagerquist, William J. Zaragoza, Bertram G. Lee, Jaszemyn C. Yambao, Beatriz Quiñones
Thirty-five environmental isolates of Shiga toxin-producing Escherichia coli (STEC) were analyzed by MALDI-TOF-TOF mass spectrometry, top-down/middle-down proteomics and DNA sequencing. Clinically-relevant Shiga toxin 2 (Stx2) produced by these STEC strains were subtyped based on MS and MS/MS (tandem mass spectrometry) of the intact B-subunit (top-down) and A2 fragment (middle-down) of the A-subunit
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Comparison of four clinically validated testosterone LC-MS/MS assays: Harmonization is an attainable goal Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-12-01 Deborah French, Julia Drees, Judith A. Stone, Daniel T. Holmes, J. Grace van der Gugten
Introduction Immunoassays and liquid chromatography-tandem mass spectrometry assays are commonly employed in clinical laboratories for measurement of total testosterone in serum. Results obtained from either of these methodologies compare poorly due to differences in calibration and/or inadvertent detection of interfering substances by the immunoassays. Standardization efforts are underway, but recent
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Thyrotoxicosis due to 1000-fold error in compounded liothyronine: A case elucidated by mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-11-30 Wajid Khan, Grace Van Der Gugten, Daniel T. Holmes
Background Thyrotoxicosis attributable exclusively to triiodothyronine (T3) is, by necessity, caused by accidental or intentional ingestion of pharmaceutical preparations. The clinical presentation of T3 overdose appears to differ from classic thyroid storm. Case A 30-year-old female patient presented serially to the emergency department with headache, nausea and vomiting. Neurological work-up was
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A simplified, rapid LC-MS/MS assay for serum and salivary creatinine Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-11-29 Laura Bernstone, Anuradha Jayanti, Brian Keevil
In routine clinical laboratories, serum creatinine is typically measured on automated analyzers using colorimetric or enzymatic assays, which are both susceptible to interferences that can lead to incorrect measurement. Here, we present a straightforward and rapid LC-MS/MS assay for serum creatinine using methanol extraction, with separation performed using a strong cation exchange column. Results
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A fully automated high-throughput liquid chromatography tandem mass spectrometry method for measuring creatinine in urine Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-11-19 Neelam Zahoor, Uliana Danilenko, Hubert W. Vesper
Reliable creatinine measurements are important to evaluate kidney function and for creatinine correction to reduce biological variability of other urinary analytes. A high-throughput, accurate liquid chromatography tandem mass spectrometry method for quantitation of human urinary creatinine has been developed and validated. Sample preparation was fully automated including cryovial decapping, sample
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Association of PTHrP levels in CSF with Alzheimer’s disease biomarkers Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-10-09 Mark M. Kushnir, Wojciech Michno, Alan L. Rockwood, Kaj Blennow, Frederick G. Strathmann, Jörg Hanrieder
Background Parathyroid hormone-related protein (PTHrP) is involved in intracellular calcium regulation, neural cell proliferation and synaptic transmission. To date, no studies have been performed to evaluate the potential of PTHrP concentrations in cerebrospinal fluid (CSF) as a biomarker of brain pathophysiology. In this study we evaluated the association between CSF concentrations of PTHrP with
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Urine analysis of 28 designer benzodiazepines by liquid chromatography–high-resolution mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-08-17 Madeleine Pettersson Bergstrand, Olof Beck, Anders Helander
Hundreds of new psychoactive substances (NPS) covering most drugs-of-abuse classes have been introduced to the recreational drug market in recent years. One class of NPS drugs that has become more common recently is “designer” benzodiazepines. Due to a close structural resemblance with prescription benzodiazepines, some of these substances may elicit a positive response (i.e. cross react) in immunoassay
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Evaluation of a one-step sample preparation protocol for analysis of total serum testosterone by LC–MS/MS Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-08-10 Yuyong Ke, Alain Dury, Renaud Gonthier, Fernand Labrie
In this study, a one-step method for liquid-liquid extraction has been compared against a two-step procedure for testosterone assays in terms of accuracy, specificity, recovery, lipid removal and baseline noise, using QCs and unknown samples. The difference in accuracy was less than 5% for adult sera, while it was less than 10% for prepubescent sera. To compare specificity, the ion ratio transition
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Volumetric absorptive microsampling (VAMS) coupled with high-resolution, accurate-mass (HRAM) mass spectrometry as a simplified alternative to dried blood spot (DBS) analysis for therapeutic drug monitoring of cardiovascular drugs Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-08-04 Sangeeta Tanna, Ahmed Alalaqi, Dennis Bernieh, Graham Lawson
Here, volumetric absorptive microsampling (VAMS), used for the measurement of cardiovascular drugs, is compared against conventional dried blood spot (DBS) card sampling to evaluate adherence to prescribed medication. Volumetric absorptive microsampling (VAMS) is an attractive alternative to plasma sampling for routine drug monitoring and potentially overcomes haematocrit issues associated with quantitative
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Comparative metabolite profiling of a metastatic and primary melanoma cell line using untargeted metabolomics: A case study Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-08-03 Zhihao Yu, Ming Huang, Brian H. Clowers
Melanoma accounts for more than 60% of deaths associated with skin cancer, making its early detection through dermatological screening essential for improved treatment outcomes. Early detection and successful treatment of melanoma can dramatically increase the 5-year survival rate from 14 to 98%. To support such efforts, comprehensive identification of metabolite patterns capable of describing cancer
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Instability of 7-aminoclonazepam in frozen storage conditions Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-07-26 Jayme L. Dahlin, Athena K. Petrides
Drug monitoring of benzodiazepines is often performed in toxicology and pain management settings. During the validation of a laboratory-developed multiplex UPLC-MS/MS assay for quantifying benzodiazepines in human urine, we observed notable instability (greater than 20% nominal) in 7-aminoclonazepam (7AC) during prolonged freezing conditions by performing method comparisons and a conventional analyte
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Evaluation of a multiplex liquid chromatography-tandem mass spectrometry method for congenital adrenal hyperplasia in pediatric patients Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-07-25 Jing Cao, Marilyn Sonilal, Stephen M. Roper, Mahesheema Ali, Sridevi Devaraj
Multiplexed adrenal steroid measurement provides critical diagnostic information for patients with congenital adrenal hyperplasia (CAH) as confirmation of newborn screening (NBS) or as initial diagnosis. This study reports the implementation of an adrenal steroid profiling method with a turnaround time (TAT) of less than 24 h using liquid chromatography and tandem-mass spectrometry (LC-MS/MS). A lab-developed
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Migration from RIA to LC-MS/MS for aldosterone determination: Implications for clinical practice and determination of plasma and urine reference range intervals in a cohort of healthy Belgian subjects Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-06-15 Caroline M. Le Goff, Ana Gonzalez-Antuña, Stéphanie D. Peeters, Neus Fabregat-Cabello, Jessica G. Van Der Gugten, Laurent Vroonen, Hans Pottel, Daniel T. Holmes, Etienne Cavalier
Background Aldosterone measurement is critical for diagnosis of primary aldosteronism and disorders of the renin-angiotensin system. We developed an LC-MS/MS method for plasma and urinary aldosterone and compared it to our RIA method. We present a reference interval study for a Belgian population. Methods 68 plasma and 23 urine samples were assayed for as part of a method comparison. For the reference
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Determination of nucleosidic/tidic reverse transcriptase inhibitors in plasma and cerebrospinal fluid by ultra-high-pressure liquid chromatography coupled with tandem mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-04-25 Perrine Courlet, Dany Spaggiari, Matthias Cavassini, Renaud Du Pasquier, Susana Alves Saldanha, Thierry Buclin, Catia Marzolini, Chantal Csajka, Laurent Decosterd
Nucleoside reverse transcriptase inhibitors (NRTIs) have been the first class of antiretroviral drugs used against HIV infection. Despite NRTI-free regimens have been eagerly sought over the years in an effort for treatment simplification, NRTIs remain in most antiretroviral combination treatment. There has been generally a limited interest for their therapeutic drug monitoring, arguably because NRTIs
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Reproducibility assessment for a broad spectrum drug screening method from urine using liquid chromatography time-of-flight mass spectrometry Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-02-14 Imir G. Metushi, Michael R. Wakefield, Kara Lynch, Judy Stone, Robert L. Fitzgerald
During the reproducibility validation for a time-of-flight (TOF) high-resolution mass spectrometry (HRMS) method set up to detect 61 drugs of abuse commonly encountered in the toxicology laboratory, it was noticed that, a number of compounds were not identified correctly during the between run analysis; the most difficult compounds to identify were norpropoxyphene, morphine, norbuprenorphine, nortriptyline
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A targeted proteomics approach to amyloidosis typing Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-02-13 Matteo Conti, Irene Poppi, Thomas Matulli Cavedagna, Elena Zamagni, Ornella Leone, Barbara Corti, Agnese Milandri, Francesco Bacci, Eric Ramazzotti, Rita Mancini, Michele Cavo, Candida Cristina Quarta, Claudio Rapezzi
Background Amyloidosis is a life threatening disease caused by deposition of various types of blood serum proteins in organs and tissues. Knowing the type of protein involved is the basis of a correct diagnosis and personalized medical treatment. While the classical approach uses immunohistochemistry, in recent years, laser micro-dissection, followed by high resolution LC-MS/MS, has been shown to provide
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Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath Clin. Mass Spectrom. (IF 1.172) Pub Date : 2018-02-08 Lukas Bregy, Yvonne Nussbaumer-Ochsner, Pablo Martinez-Lozano Sinues, Diego García-Gómez, Yannick Suter, Thomas Gaisl, Nina Stebler, Martin Thomas Gaugg, Malcolm Kohler, Renato Zenobi
Background New mass spectrometry (MS) techniques analysing exhaled breath have the potential to better define airway diseases. Here, we present our work to profile the volatile organic compounds (VOCs) in exhaled breath from patients with chronic obstructive pulmonary disease (COPD), using real-time MS, and relate this disease-specific breath profile to functional disease markers. Methods In a matched
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Multiplexed therapeutic drug monitoring (TDM) of antiviral drugs by LC–MS/MS Clin. Mass Spectrom. (IF 1.172) Pub Date : 2017-12-16 M. Conti, T. Matulli Cavedagna, E. Ramazzotti, R. Mancini, L. Calza, M. Rinaldi, L. Badia, V. Guardigni, P. Viale, G. Verucchi
Background Therapeutic drug monitoring (TDM) can be a useful tool in the clinical management of anti-hepatitis C virus (anti-HCV) drugs. Methods for the determination of various types of anti-HCV drugs in biological samples are, therefore, needed for clinical laboratories. Objective In this work, employing the LC–MS/MS approach, we aimed to develop a multiplexed method for identification of the following
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