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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 μg/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.

The key to determine the performance of fuzzy inference inversion is to select a reasonable domain. However, there is no universal method for selecting domain at present. According to the characteristics of heat flux of geothermal heat source and the research of fuzzy inference inversion process, this paper modified the fuzzy inference method from two aspects of domain setting and iteration termination condition. The recommended domain and selection scheme for solving the problem of geothermal heat flux are given, and the modified fuzzy inference inversion method is applied to Rucheng geothermal field to verify the method. The results showed that the modified fuzzy inference inversion method could overcome the problem that the solution of the traditional method fell into a cycle, and the relative error of the verification term was less than 5%. Compared with the traditional method, the modified method greatly improved the computational efficiency, and the number of iterations was reduced to only 7. This method has a good application prospect for geothermal heat source inversion and resource evaluation.