Qualitative and quantitative determination of anaprazole and its major metabolites in human plasma

Publication date: Available online 4 February 2020Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Chongzhuang Tang, Liang Li, Xifeng Ma, Jin Wang, Bo Chen, Xiaojian Dai, Yifan Zhang, Xiaoyan ChenAbstractAnaprazole is a novel proton pump inhibitor under development for the treatment of gastric and duodenal ulcers. In the present study, an ultra-performance liquid chromatography-ultraviolet detector/quadrupole time-of-flight mass spectrometry method was developed for the metabolic profiling of human plasma after an oral administration of 40 mg anaprazole. The principal metabolic pathways were identified as sulfoxide reduction to thioether (M8-1), dehydrogenation (M21-1), sulfoxide oxidation to sulfone (M16-3), and sulfoxide reduction with O-demethylation to form carboxylic acid (M7-1). Anaprazole, M8-1, M16-3, M21-1, and M7-1 were selected and further quantified in human plasma by using a rapid and sensitive liquid chromatography–tandem mass spectrometry method. Anaprazole and its four metabolites were extracted from 50 of μL plasma by acetonitrile protein precipitation. Chromatographic retention and separation were achieved on an Kinetex XB-C18 column (50 mm × 4.6 mm i.d., 5 μm) under gradient elution using 5 mM ammonium acetate with 0.005% ammonium hydroxide and methanol with 0.005% ammonium hydroxide as the mobile phase. Positive electrospray ionization was performed using multiple reaction monitoring with transitions of m/z 402.2→242...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research