Esta es la versión de autor del artículo publicado en: This is an author produced version of a paper published in:Therapeutic Drug Monitoring 37.3 (2015) Omeprazole (OME) is a proton pump inhibitor (PPI) with 58% bioavailability after single oral dose, presenting large inter-individual variations and significant drug-drug interactions. A simple and rapid liquid chromatography in tandem with mass spectrometry (LC/MS-MS) with solid phase extraction (SPE) and isotope-labelled internal standard (IS) method was developed to monitor the plasma levels of OME for application in pharmacokinetics and drug-drug interactions studies. OME and its IS (OME-D3), were eluted with Zorbax extend C-18 rapid resolution (4.6 mm x 50 mm, 3.5 μm) at 25ºC, under isocratic conditions through a mobile phase consisting of 1 mM ammonium acetate, pH 8.5 (55%), and acetonitrile (ACN, 45%). The flow rate was 0.8 mL/min and the run time of chromatogram was 1.2 min. OME was detected and quantified by LC-MS/MS with positive electrospray ionization (ESI) that operates in multiple-reaction monitoring (MRM) mode. The method was linear in the range of 1.5-2000 ng/mL for OME. The validation assays of accuracy and precision, matrix effect, extraction recovery and stability of the samples for OME did not deviate more than 20% for the lower limit of quantification (LLOQ) and no more than 15% for other quality controls (QCs), according to regulatory agencies.
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AbstractOmeprazole (OME) is a proton pump inhibitor (PPI) with 58% bioavailability after a single oral dose. It is subject to marked inter-individual variations and significant drugdrug interactions. The authors developed a simple and rapid method based on liquid chromatography in tandem with mass spectrometry (LC/MS-MS) with solid phase extraction (SPE) and isotope-labelled internal standard (IS) to monitor plasma levels of OME in pharmacokinetics and drug-drug interaction studies. OME and its IS (OME-D3) were eluted with the Zorbax Extend C-18 rapid resolution column (4.6 mm x 50 mm, 3.5 μm) at 25ºC, under isocratic conditions through a mobile phase consisting of 1 mM ammonium acetate, pH 8.5 (55%), and acetonitrile (ACN, 45%). The flow rate was 0.8 mL/min, and the chromatogram run time was 1.2 min. OME was detected and quantified by LC-MS/MS with positive electrospray ionization (ESI), which operates in multiple-reaction monitoring (MRM) mode. The method was linear in the range of 1.5-2000 ng/mL for OME. The validation assays for accuracy and precision, matrix effect, extraction recovery, and stability of the samples for OME did not deviate more than 20% for the lower limit of quantification (LLOQ) and no more than 15% for other quality controls (QCs). These findings are consistent with the requirements of regulatory agencies.