Metabolites identification and pharmacokinetic profile of hirsuteine, a bioactive component in Uncaria in rats by ultra‐high performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry

Hirsuteine is one of the major bioactive tetracyclic indole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks, possessing a wide range of pharmacological activities including neuroprotective, anticonvulsant, antihypertensive, sedative and hypnotic, and so forth. The present study was undertaken to assess the metabolism and plasma pharmacokinetics of hirsuteine in rats. After oral administration of hirsuteine at the dose of 30 mg/kg, 13, 21, and 8 metabolites were detected in rat plasma, urine, and bile by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, respectively. Furthermore, plasma concentrations of hirsuteine and its four metabolites, 4-hirsuteine N-oxide, 3,4-dehydrohirsuteine, 11-hydroxyhirsuteine, and 11-hydroxyhirsuteine-11-O-glucuronide were simultaneously quantified in rat plasma, using carbamazepine as the internal standard. The linear calibration curve of hirsuteine was in the concentration range of 0.005-5.0 mu g/ml. The lower limit of quantitation in the rat plasma was 5 ng/ml for hirsuteine. This study is the first to comprehensively investigate the metabolism process of hirsuteine and the pharmacokinetic profiles of hirsuteine and its major metabolite, and will provide a scientific basis to further elucidate the pharmacodynamic material basis and therapeutic mechanism of Uncaria prescriptions.