@article{3026266, title = "Study of the effect of CYP2C19 polymorphisms on omeprazole pharmacokinetics by utilizing validated LC–MS/MS and Real Time-PCR methods", author = "Koukoula, M. and Dotsikas, Y. and Molou, E. and Schulpis, K.H. and Thodi, G. and Chatzidaki, M. and Triantafylli, O. and Loukas, Y.L.", journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences", year = "2017", volume = "1047", pages = "173-179", publisher = "Elsevier B.V.", doi = "10.1016/j.jchromb.2016.06.046", keywords = "Biological materials; Blood; Electrospray ionization; Liquid chromatography; Liquids; Mass spectrometry; Pharmacokinetics, Dried blood spots; LC-MS/MS; Liquid chromatography tandem mass spectrometry (LC MS/MS); Multiple reaction monitoring; Omeprazole; Pharmacogenetic; Positive electrospray ionization; Real-time polymerase chain reaction (real-time PCR), Polymerase chain reaction, cytochrome P450 2C19; omeprazole; antiulcer agent; cytochrome P450 2C19; omeprazole, Article; bioequivalence; blood sampling; controlled study; dried blood spot testing; drug determination; electrospray mass spectrometry; female; genetic polymorphism; genotype; genotype phenotype correlation; human; liquid chromatography-mass spectrometry; liquid liquid extraction; male; multiple reaction monitoring; normal human; plasma volume; priority journal; real time polymerase chain reaction; tablet formulation; blood; genetics; high performance liquid chromatography; procedures; real time polymerase chain reaction; tandem mass spectrometry; validation study, Anti-Ulcer Agents; Chromatography, High Pressure Liquid; Cytochrome P-450 CYP2C19; Genotype; Humans; Liquid-Liquid Extraction; Omeprazole; Polymorphism, Genetic; Real-Time Polymerase Chain Reaction; Tandem Mass Spectrometry", abstract = "A fully automated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed for the determination of omeprazole in human plasma. Utilization of 96-well plates and robotic liquid handling workstations, rendered the whole procedure very fast, compared to the manual respective procedure of Liquid-Liquid Extraction (LLE). Sample analysis was performed by reversed phase LC–MS/MS, with positive electrospray ionization, using multiple reaction monitoring (MRM). The method required low plasma volumes and analysis of samples was completed in short run times. It was fully validated and applied to a pharmacokinetic study after per os administration of 20 mg tablet formulations of omeprazole. The obtained concentrations were used for the calculation of the basic omeprazole pharmacokinetic parameters. Some variations observed in pharmacokinetic parameters among subjects were attributed to differences of CYP2C19 genotype. Therefore, a novel molecular method was developed in which DNA analysis was conducted by using Real Time-Polymerase Chain Reaction (Real Time-PCR). As source of biological material, Dried Blood Spots (DBS) were utilized, offering an alternative and advantageous strategy for such kind of studies. © 2016 Elsevier B.V." }