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A sensitive LC–MS/MS method for the determination of triptolide and its application to pharmacokinetic research in rats
Author(s) -
Xu Ye,
Chen Xiaoyan,
Zhong Dafang
Publication year - 2019
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4422
Subject(s) - triptolide , chemistry , chromatography , benzylamine , tripterygium wilfordii , derivatization , selected reaction monitoring , pharmacokinetics , triple quadrupole mass spectrometer , detection limit , mass spectrometry , analyte , electrospray ionization , tandem mass spectrometry , pharmacology , biochemistry , organic chemistry , medicine , apoptosis , alternative medicine , pathology
Triptolide is one of the main active ingredients of Tripterygium wilfordii Hook. F. In this study, a sensitive LC–MS/MS method was established and validated to determine the concentration of triptolide in rat plasma. Triptolide and an internal standard [(5 R )‐5‐hydroxytriptolide] were extracted from 100 μL of rat plasma with acetonitrile, and the dried residue was then reconstituted and reacted with benzylamine to produce benzylamine triptolide and benzylamine (5 R )‐5‐hydroxytriptolide. Derivatization increased the sensitivity of triptolide detection by ~100‐fold. Quantification was performed using a QTRAP 5500 tandem mass spectrometer with positive electrospray ionization in multiple reaction monitoring mode with an ion transition m / z 468.5 → 192.0 for benzylamine triptolide and m / z 484.3 → 192.1 for benzylamine (5 R )‐5‐hydroxytriptolide. Good linearity was observed in the range of 0.030–100 ng/mL with a lower limit of quantitation of 0.030 ng/mL. The intra‐ and inter‐day precision was <6.5%, and the accuracy ranged from −11.7 to −4.4%. The recovery remained consistent and was reproducible at different concentrations. This method was successfully applied to the study of triptolide drug–drug interactions in Sprague–Dawley rats. With the use of itraconazole (40 mg/kg, p.o.) as a CYP3A inhibitor, the plasma exposure of triptolide in rats was increased by 36%.