Simultaneous determination of sinomenine and its metabolites desmethyl‐sinomenine and sinomenine N‐oxide in rat plasma by liquid chromatography tandem mass spectrometry

Sinomenine is an active ingredient extracted from herb medicine, which has been prescribed to treat rheumatoid arthritis in clinics. The present work was to develop a simple method to simultaneously determine sinomenine and its metabolites desmethyl sinomenine and sinomenine N‐oxide in rat plasma by liquid chromatography tandem mass spectrometry. Precursor‐to‐product transitions for detection were m/z 330.2 > 239.1 for sinomenine, m/z 316.2 > 239.1 for desmethyl‐sinomenine, m/z 346.2 > 314.1 for sinomenine N‐oxide and m/z 286.2 > 153.2 for morphine (internal standard), respectively. During the validation and sample quantification, an excellent linear calibration range was observed for all the analytes with correlation coefficients more than 0.999 (r > 0.99). The extraction recovery was more than 85%. No significant matrix effect and carryover were observed. The precision was less than 6.45%, whereas accuracy ranged from –4.10% to 7.23%. The validated method has been successfully applied to the pharmacokinetic study of sinomenine, desmethyl sinomenine, and sinomenine N‐oxide in rat plasma after oral administration of sinomenine at a single dose of 5 mg/kg. The results suggested that sinomenine was rapidly metabolized into its metabolite desmethyl sinomenine and sinomenine N‐oxide.