title: Validation of a chiral liquid chromatography-tandem mass spectrometry method for the determination of pantoprazole in dog plasma.
abstract: Pantoprazole (PAN), a selective proton pump inhibitor, is used clinically as a racemic mixture for the treatment of acid-related gastrointestinal disorders. To investigate its stereoselective pharmacokinetics, a chiral liquid chromatography-tandem mass spectrometry method was developed and validated to determine the pantoprazole enantiomers in dog plasma. After liquid-liquid extraction, a baseline resolution of enantiomers was achieved on an ovomucoid column using the mobile phase of methanol:acetonitrile:10mM ammonium formate (pH 7) (10.4:2.6:87, v/v/v) at 30°C within 10min. Stable isotopically labeled (+)-d(3)-pantoprazole and (-)-d(3)-pantoprazole were used as internal standards. Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode via positive atmospheric pressure chemical ionization. The method was linear in the concentration range of 20.0-10,000ng/mL for each enantiomer using 25μL of dog plasma. The lower limit of quantification (LLOQ) for each enantiomer was 20.0ng/mL. Intra- and inter-day precision ranged from 3.2% to 10.3% for (+)-pantoprazole and 3.7-10.0% for (-)-pantoprazole. Accuracy varied from -1.4% to -0.2% for (+)-pantoprazole and -1.6% to 0.8% for (-)-pantoprazole. The validated method was applied successfully for stereoselective pharmacokinetic studies of racemic pantoprazole.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Meixia
authors.initials: M
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Ma
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Dafang
authors.initials: D
authors.lastname: Zhong
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Chen
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood* / Q000737:chemistry; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs / Q000097:blood*; D004355:Drug Stability; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D000077402:Pantoprazole; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000077402:Pantoprazole