Determination of cryptotanshinone and its metabolite in rat plasma by liquid chromatography–tandem mass spectrometry

A sensitive and selective LC–MS–MS method has been developed and validated for the determination of cryptotanshinone (CTS) and its active metabolite tanshinone II A (TS II A) in rat plasma using fenofibrate (FOFB) as internal standard. Liquid–liquid extraction was used for sample preparation. Chromatographic separation was achieved on a Waters symmetry ODS column using methanol and water (85:15) as mobile phase delivered at 1.0 mL/min. LC–MS–MS analysis was carried out on a Finnigan LC-TSQ Quantum mass spectrometer using atmospheric pressure chemical ionization (APCI) and positive multiple reaction monitoring. Ions monitored were m/z 297.0 → 251.0 for CTS, m/z 295.0 → 249.0 for TS II A, and m/z 361.1 → 233.0 for FOFB with argon at a pressure of 0.2 Pa and collision energy of 25 eV for collision-induced dissociation (CID). The assay was linear over the range 0.1–20 ng/mL for CTS and 0.2–15 ng/mL for TS II A. The average recoveries of CTS and TS II A from rat plasma were 93.7 and 94.7%, respectively. The established method has been applied in a pharmacokinetic study of CTS in rats.