Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
4 years ago

Simultaneous determination of gentiopicroside and its two active metabolites in rat plasma by LC–MS/MS and its application in pharmacokinetic studies

Gentiopicroside is a natural secoiridoid glycoside that may require metabolic activation to exert pharmacological effects. In this study, two active metabolites of gentiopicroside (M1 and M2) were isolated from rat urines and identified with our previous method. Most importantly, a fast, sensitive and selective ultra high-performance liquid chromatography–tandem mass spectrometry method was developed to simultaneously determine gentiopicroside and its two metabolites in rat plasma. The analytes and internal standard (swertiamarin) were separated on an ACQUITY UPLC® BEH C18 column (2.1×50mm, 1.7μm) using gradient elution by acetonitrile and 0.1% formic acid at a flow rate of 0.4mL/min. The mass spectrometry detector was operated in the multiple reaction monitoring with positive ionization mode. The method had a good linearity over the concentration range of 0.2–10,000ng/mL for gentiopicroside and 0.1–5000ng/mL for the two metabolites. The validated method was successfully applied to the pharmacokinetic study of gentiopicroside and its metabolites after single oral administration of gentiopicroside (150mg/kg) to rats (n=8). The pharmacokinetic differences between gentiopicroside and its two metabolites were identified.Results provided the evidence for in vivo metabolism-based activation of gentiopicroside.

Publisher URL: www.sciencedirect.com/science

DOI: S1570023217312953

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