Wojnicz Aneta, Gil García Ana Isabel, Román-Martínez Manuel, Ochoa-Mazarro Dolores, Abad-Santos Francisco, Ruiz-Nuño Ana
*Instituto Teófilo Hernando; †Departamento de Farmacología y Terapéutica, Facultad de Medicina; and ‡Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain.
Ther Drug Monit. 2015 Jun;37(3):381-8. doi: 10.1097/FTD.0000000000000155.
Omeprazole (OME) is a proton pump inhibitor with a 58% bioavailability after a single oral dose. It is subject to marked interindividual variations and significant drug-drug interactions. The authors developed a simple and rapid method based on liquid chromatography in tandem with mass spectrometry with solid phase extraction and isotope-labeled internal standard to monitor plasma levels of OME in pharmacokinetics and drug-drug interaction studies.
OME and its internal standard (OME-D3) were eluted with a Zorbax Extend C-18 rapid resolution column (4.6 × 50 mm, 3.5 μm) at 25°C, under isocratic conditions through a mobile phase consisting of 1 mM ammonium acetate, pH 8.5 (55%), and acetonitrile (45%). The flow rate was 0.8 mL/min, and the chromatogram run time was 1.2 minutes. OME was detected and quantified by liquid chromatography in tandem with mass spectrometry with positive electrospray ionization, which operates in multiple-reaction monitoring 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 and no more than 15% for other quality controls.
These findings are consistent with the requirements of regulatory agencies. The method enables rapid quantification of OME concentrations and can be used in pharmacokinetic and drug-drug interaction studies.
