RESUMO
Delsoline, a major alkaloid of Delphinium anthriscifolium Hance, has both a curare-like effect and a ganglion-blocking effect and is used to relieve muscle tension or hyperkinesia. A ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for the determination of delsoline in mouse blood, and the pharmacokinetics of delsoline after intravenous administration (1 mg/kg) and intragastric administration (9, 6, and 3 mg/kg) were studied. Gelsenicine served as an internal standard, and a UPLC BEH C18 chromatographic column was used. The mobile phase consisted of acetonitrile and 0.1% formic acid; the gradient elution flow rate was 0.4 mL/min. The MRM model was used for the quantitative analysis of delsoline m/z 468.3â¶108.1 and the internal standard m/z 327.1â¶296.1. Mouse blood samples were treated with acetonitrile precipitation to remove proteins. In the concentration range of 0.1-1000 ng/mL, delsoline in mouse blood showed a good linearity (r 2 > 0.995), and the lower limit of quantitation was 0.1 ng/mL. The intraday precision relative standard deviation (RSD) was below 14%, and the interday precision RSD was below 15%. The accuracy ranged between 94.3% and 110.1%, the average recovery was above 90.8%, and the matrix effect ranged between 97.0% and 102.5%. The UPLC-MS/MS method was sensitive, rapid, and selective in the study of pharmacokinetics of delsoline. The absolute bioavailability of delsoline was 20.9%.
RESUMO
In order to investigate the effects of Zhu-tan Tong-luo decoction on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6. The rats were randomly divided into acute Zhu-Tan Tong-Luo decoction group (Low, High), chronic Zhu-Tan Tong-Luo decoction group (Low, High) and control group. The acute group rats were given 0.6, 1.2 g/kg (Low, High) Zhu-tan Tong-luo decoction by intragastric administration for 1 day, and the chronic group for 14 days. Six probe drugs bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. There statistical pharmacokinetics differences for omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol in rats were observed by comparing acute Zhu-tan Tong-luo decoction group with control group; and statistical pharmacokinetics differences for bupropion, omeprazole, phenacetin, testosterone, tolbutamide, and metroprolol were observed by comparing chronic Zhu-Tan Tong-Luo decoction group with control group. After intragastric administration of Zhu-Tan Tong-Luo decoction may slightly induce the activities of CYP2B6, CYP2C19, CYP1A2, CYP3A4, CYP2C9, CYP2D6 of rats. Induction of drug metabolizing enzyme by Zhu-Tan Tong-Luo decoction would reduce the efficacy of other drug. Additional, there no statistical difference for biochemical results after 1 or 14 intragastric administration of Zhu-Tan Tong-Luo decoction.