title: A bio-analytical hydrophilic interaction LC-MS/MS method for the simultaneous quantification of omeprazole and lansoprazole in human plasma in support of a pharmacokinetic omeprazole study in children.
abstract: A hydrophilic interaction LC method with MS/MS was developed and validated for the simultaneous quantification of omeprazole and lansoprazole in human plasma. Chromatographic separation was achieved on a Betasil silica column using a high organic mobile phase (eluent A: ACN/formic acid 997.5:2.5 v/v; eluent B: water/formic acid 997.5:2.5 v/v) and gradient elution. The mass spectrometer was operated in the Multiple Reaction Monitoring mode. Prior to chromatography, liquid-liquid extraction with ethyl acetate was used and the organic layer was diluted with ACN, allowing direct injection on column. The method showed acceptable linearity, high precision (RSD%<10.5%), accuracy (88.9-109.3%) and selectivity in the two concentration ranges studied: 1.5-100 and 5-2000 ng/mL. The LOQ was established at 1.5 and 5 ng/mL for the two concentration ranges. Lack of variability in matrix effects was demonstrated and mean extraction recovery for omeprazole and lansoprazole was determined in the low (56.3-67.7%) and high (45.3-44.3%) concentration range, respectively. Additionally, plasma samples were found to be stable after three freeze-thaw cycles and for at least 15 h after extraction. This assay was successfully applied to a pharmacokinetic omeprazole study in children with cerebral palsy and mental retardation.
authors.affiliation: Laboratory of Medical Biochemistry and Clinical Analysis, Ghent University, Ghent, Belgium. Julie.DeSmet@UGent.be
authors.forename: Julie
authors.initials: J
authors.lastname: De Smet
authors.forename: Koen
authors.initials: K
authors.lastname: Boussery
authors.forename: Pieter
authors.initials: P
authors.lastname: De Cock
authors.forename: Peter
authors.initials: P
authors.lastname: De Paepe
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Myriam
authors.initials: M
authors.lastname: Van Winckel
authors.forename: Jan
authors.initials: J
authors.lastname: Van Bocxlaer
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood* / Q000493:pharmacokinetics; D000897:Anti-Ulcer Agents / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D064747:Lansoprazole; D057230:Limit of Detection; D009853:Omeprazole / Q000097:blood* / Q000493:pharmacokinetics; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D064747:Lansoprazole; D009853:Omeprazole