title: Improvement and validation of a high-performance liquid chromatography in tandem mass spectrometry method for monitoring of omeprazole in plasma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *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.
authors.forename: Aneta
authors.initials: A
authors.lastname: Wojnicz
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Gil García
authors.forename: Manuel
authors.initials: M
authors.lastname: Román-Martínez
authors.forename: Dolores
authors.initials: D
authors.lastname: Ochoa-Mazarro
authors.forename: Francisco
authors.initials: F
authors.lastname: Abad-Santos
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Nuño
mesh_terms: D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D009853:Omeprazole / Q000097:blood*; D052616:Solid Phase Extraction; D053719:Tandem Mass Spectrometry
chemical_list: D009853:Omeprazole