A sensitive LC–MS/MS method for simultaneous quantification of geniposide and its active metabolite genipin in rat plasma and its application to a pharmacokinetic study. (21st November 2017)

• Record Type: Journal Article
• Authors: Shi, Fuguo; Pan, Hong; Li, Yi; Huang, Linyan; Wu, Qin; Lu, Yuanfu
• Is Part Of: Biomedical chromatography. Volume 32:Number 3(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-11-21
• Subjects: genipin -- geniposide -- instability -- LC–MS/MS -- pharmacokinetics; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.4126
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: Genipin (GP), an active metabolite of geniposide (GE), exhibits more potent pharmacological effects than its parent compound. In this paper, a sensitive LC‐MS/MS method was developed and fully validated for the simultaneous determination of GE and GP in rat plasma. We found that GP degraded rapidly in rat plasma at room temperature as a result of irreversible binding with the endogenous nucleophiles in plasma. GP was stable when the sample's pH was ≤4.0. The degradation of GP in rat plasma was well prevented by immediate addition of 5% glacial acetic acid to the freshly collected plasma. The detection was performed on a tandem mass spectrometer coupled with electrospray ionization source in negative mode. Quantification was conducted by multiple reaction monitoring of the transitions [M + CH3 COO] − m/z 447.3 → 225.3 for GE and [M − H] − m/z 225.2 → 123.1 for GP. The method exhibited high sensitivity (LLOQ 1 ng/mL for GE and 0.2 ng/mL for GP) by selecting the acetate adduct ions as the precursor ions for GE. The robust developed method was successfully applied to a pharmacokinetic study in rats after oral administration of GE.