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Scientific article
Open access
English

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

Published inJournal of chromatography. B, vol. 1232, 123962
Publication date2024-01-01
First online date2023-12-09
Abstract

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 C18trapping 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.

eng
Keywords
  • 5-Hydroxy-omeprazole
  • CYP2C19
  • Omeprazole
  • Phenotype
  • Stereoselective
  • Humans
  • Chromatography, Liquid
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP2C19
  • Tandem Mass Spectrometry
  • Cellulose
  • 2-Pyridinylmethylsulfinylbenzimidazoles
Citation (ISO format)
ABOUIR, Kenza et al. Stereoselective separation of omeprazole and 5-hydroxy-omeprazole using dried plasma spots and a heart-cutting 2D-LC approach for accurate CYP2C19 phenotyping. In: Journal of chromatography. B, 2024, vol. 1232, p. 123962. doi: 10.1016/j.jchromb.2023.123962
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Identifiers
ISSN of the journal1570-0232
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Technical informations

Creation02/06/2024 9:04:58 AM
First validation05/14/2024 8:14:53 AM
Update time05/14/2024 8:14:53 AM
Status update05/14/2024 8:14:53 AM
Last indexation05/14/2024 8:15:14 AM
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