Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping

Article Article scientifique Article Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping eng 2023-12-09 2024-01-01 author Abouir Kenza Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland; School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland. Electronic address: Kenza.abouir@unige.ch. 820243 author Samer Caroline Flora 0000-0001-8178-0616 Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland; School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Caroline.samer@hcuge.ch. 105661 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) author Landry Romain Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Romain.landry@etu.unige.ch. 943766 author Varesio Emmanuel School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland. Electronic address: Emmanuel.varesio@unige.ch. 30230 Section des sciences pharmaceutiques (FARMA) author Daali Youssef Division of Clinical Pharmacology and Toxicology, Geneva University Hospitals, Geneva, Switzerland; School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Geneva, Switzerland; Faculty of Medicine, University of Geneva, Geneva, Switzerland. Electronic address: Youssef.daali@hcuge.ch. 46042 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) 123962 10.1016/j.jchromb.2023.123962 38096743 1570-0232 https://www.sciencedirect.com/science/article/pii/S1570023223003720 Omeprazole (OME) is a widely used gastric proton pump inhibitor, marketed as a racemic mixture comprising (S)- and (R)-enantiomers, with distinct pharmacokinetic profiles. OME is primarily metabolized by the cytochrome P450 enzymes 2C19 (CYP2C19) and 3A4 (CYP3A4). OME is a conventional probe for CYP2C19 phenotyping. Accurate measurement of these enantiomers and their metabolites is essential for pharmacokinetic studies. This article presents a sensitive and accurate two-dimensional liquid chromatography-mass spectrometry (LC-MS/MS) method for the simultaneous quantification of OME enantiomers and its hydroxylated metabolite (5-hydroxyomeprazole) in human plasma. The method involves an online extraction using an achiral Discovery HS C<sub>18</sub>trapping column for purification (20 × 2.1 mm ID, 5μm particle size, Supelco) and subsequent forward flush elution onto a chlorinated phenylcarbamate cellulose-based chiral column (150x2mm ID, 3 μm particle size, Lux Cellulose-4, Phenomenex). The assay was fully validated and met international validation criteria for accuracy, precision, and stability and ensured high selectivity and sensitivity within a short runtime (<8 min). Application of this method to clinical samples demonstrated its utility in studying OME enantiomer pharmacokinetics, particularly its potential for phenotyping the activity of the CYP2C19 isoenzyme. This robust analytical approach offers a valuable tool for clinicians and researchers studying OME's pharmacokinetics, providing insights into its metabolism and potential implications for personalized medicine. 5-Hydroxy-omeprazole CYP2C19 Omeprazole Phenotype Stereoselective Humans Chromatography, Liquid Aryl Hydrocarbon Hydroxylases / metabolism Cytochrome P-450 CYP2C19 Tandem Mass Spectrometry Cellulose 2-Pyridinylmethylsulfinylbenzimidazoles Dewey 615 Dewey 617 31 Section des sciences pharmaceutiques 17 63 Département d'anesthésiologie, pharmacologie, soins intensifs et urgences 229 false 1280 Pharmaco-omiques et médecine de précision 1003 Journal of chromatography. B 1232 7fdd469c-9d0f-4649-af71-1240643997d0 Article (Published version) Public 1-s2.0-S1570023223003720-main.pdf 3710166 application/pdf CC BY-4.0 71044017041dbd49eff2e29beaa09d7365b649c873da38bd37f463e62513780d 03e976f2-9e8d-4536-8a1a-8e72df4c6505 Supplemental data Public 1-s2.0-S1570023223003720-mmc1.docx 1369505 application/vnd.openxmlformats-officedocument.wordprocessingml.document 945fc6480bb451ee43fae25be2ee2456c44e7e358ce19aa715287d2a87cc022a openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département d'anesthésiologie, pharmacologie, soins intensifs et urgences

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Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping	Journal of chromatography. B			2024	110	123

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