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Establishment of a rapid and sensitive UPLC-MS/MS method for pharmacokinetic determination of nine alkaloids of crude and processed Corydalis turtschaninovii Besser aqueous extracts in rat plasma

Tao, Yi, Huang, Surun, Yan, Jizhong, Cai, Baochang
Journal of chromatography 2019 v.1124 pp. 218-225
Corydalis, Oriental traditional medicine, absorption, acetonitrile, alkaloids, analgesic effect, bioavailability, chromatography, formic acid, methanol, pain, pharmacokinetics, rats, tandem mass spectrometry, therapeutics
Corydalis turtschaninovii (CT) is a traditional Chinese medicine which is known to have analgesic effects, and is under investigation for the management of chronic pain. Our study aims to establish a UPLC–MS/MS method for pharmacokinetic determination of nine bioactive alkaloids of raw and processed CT in rat plasma. Nitidine chloride was selected as internal standard. After protein precipitation with methanol, the plasma samples were separated on a reversed phased column with a mobile phase of acetonitrile and water (including 0.1% formic acid). The MRM parameters were optimized as follows: m/z 354.0 → 188.1 for protopine, m/z 321.0 → 293.1 for coptisine, m/z 371.1 → 189.1 for allocryptopine, m/z 357.1 → 193.3 for tetrahydropalmatine, m/z 324.1 → 176.1 for tetrahydrocoptisine, m/z 340.1 → 176.2 for tetrahydroberberine, m/z 368.1 → 289.1 for corynoline, m/z 370.5 → 192.1 for corydaline, m/z 367.2 → 351.2 for dehydrocorydaline, and m/z 406.0 → 300.3 for the IS. The linearity, accuracy, precision, stability, recovery and matrix effect of the method were well validated. This method was successfully employed for a pharmacokinetic study of raw and vinegar-processed CT in rats. The absorption of the nine alkaloids was accomplished in an hour. The double peak phenomenon of the nine alkaloids may be ascribed to enterohepatic recirculation. Compared with the raw group, AUC0→t and Cmax of the nine alkaloids were significantly elevated in the vinegar-processed group. Our findings suggest that vinegar-processing could increase the bioavailability of the nine alkaloids of CT in rats. The pharmacokinetic information obtained will provide basis for application of processed CT in future clinical therapy.