Journal
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
Volume 70, Issue -, Pages 624-630Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jpba.2012.06.026
Keywords
Triptolide; LC-MSn; Rat liver microsome; Rat intestinal flora; Metabolite
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Funding
- National Natural Science Foundation of China [30630075]
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Triptolide, a major active constituent of Tripterygium wilfordii Hook F, has multiple pharmacological activities. In this work, a rapid, sensitive and specific liquid chromatography coupled to an ion trap mass spectrometer (MS) with electrospray ionization (ESI) interface has been developed for identification of triptolide and some of its metabolites in rat urine after oral administration of a single dose (0.6 mg/kg) of triptolide to healthy rats, as well as some metabolites in vitro after incubation with rat liver microsome (RLM) and rat intestinal flora, respectively. All samples were separated on a reversed-phase 08 column using a mobile phase of acetonitrile/water (70:30, v/v) and detected by an on-line MSn detector. Identification and structural elucidation of the selected metabolites were performed by comparing their full scan MSn spectra with those of the parent drug. In this paper we identified ten metabolites in rat urine, four metabolites in RLM incubation solution and one metabolite in rat intestinal flora incubation solution, after drug administration. The metabolic reactions of triptolide that we observed in vivo were hydrolysis reaction, hydroxylation reaction, and the conjugate reaction with sulfate, glucuronide and GSH, respectively. The in vitro metabolic reactions of triptolide observed were hydrolysis and hydroxylation reactions. (C) 2012 Elsevier B.V. All rights reserved.
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