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Li Y.-X.,Chengdu University of Traditional Chinese Medicine | Li Y.-X.,The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine | Li Y.-X.,State Key Laboratory Breeding Base of Systematic Research | Gong X.-H.,Chengdu University of Traditional Chinese Medicine | And 17 more authors.
Biomedical Chromatography | Year: 2014

A specific and sensitive UHPLC-qTOF-MS method was developed and validated for quantification of fuziline in rat plasma after oral administration of three dosages. The analyte was separated on an Acquity UPLC BEH C18 column with a total running time of 3min using a mobile phase of 0.1% formic acid aqueous solution and methanol (80:20, v/v) at a flow-rate of 0.25mL/min. The calibration curves for fuziline showed good linearity in the concentrations ranging from 1 to 200ng/mL with correlation coefficients >0.997. The precision, accuracy, recovery and stability were deemed acceptable. The method was applied to a pharmacokinetics study of fuziline in rats. The mean half-life was 5.93, 6.13 and 5.12h for 1, 2 and 4mg/kg oral administration of fuziline, respectively. The peak concentration and area under the concentration-time curve increased linearly with the doses. The sum of these results indicated that, in the range of the doses examined, the pharmacokinetics of fuziline in rat was based on first-order kinetics. © 2014 John Wiley & Sons, Ltd. Source


Li Y.,Chengdu University of Traditional Chinese Medicine | Li Y.,The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine | Li Y.,State Key Laboratory Breeding Base of Systematic Research | Li Y.-X.,Chengdu University of Traditional Chinese Medicine | And 14 more authors.
European Journal of Drug Metabolism and Pharmacokinetics | Year: 2016

Background and Objectives: Aconitum carmichaelii Debx. (Fuzi) is usually compatible with Rheum palmatum L. (Dahuang) in clinic. The study is conducted to investigate the influence of Dahuang on the pharmacokinetics of Fuzi. Methods: Twelve rats were randomly divided into two groups. Fuzi group was orally administered a single dose of 38.4 mg/kg total alkaloids from Fuzi, and Fuzi–Dahuang group was given 38.4 mg/kg total alkaloids from Fuzi and 76.8 mg/kg Dahuang anthraquinones at the same time. The plasma concentrations of aconitine (AC), mesaconitine (MC), and hypaconitine (HC), benzoylaconine (BAC), benzoylmesaconine (BMC), benzoylhypaconine (BHC), and aconine (ACN) were determined by ultra-performance liquid chromatography–quadrupole time of flight mass spectrometry method. The pharmacokinetic parameters were calculated including maximum plasma concentration (Cmax), area under the plasma concentration–time curve in all time-points (AUClast), apparent volume of distribution (Vz/F), apparent plasma clearance (CL/F), elimination half-life (T1/2), and time to achieve maximum concentration (Tmax). Results: AUClast of diester diterpene alkaloids (DDAs) were 58.20, 169.78, 278.48 ng·h/mL for AC, MC, and HC in Fuzi–Dahuang group which were remarkably lower than that in Fuzi group (71.62, 183.13, 410.59 ng·h/mL for AC, MC, HC). CL/F was significantly increased from 173.88 to 218.85 mL/h for AC, 433.22 to 800.21 mL/h for MC, 1150.61 to 1307.30 mL/h for HC after combination. However, with the significantly increased Cmax, AUClast of monoester diterpene alkaloids (MDAs) and amine diterpenoid alkaloids (ADAs) were 152.42, 1238.95, 287.96, 123.33 ng·h/mL for BAC, BHC, BMC, ACN in Fuzi–Dahuang group which were remarkably higher than that in Fuzi group (54.47, 1105.48, 200.75, 86.48 ng·h/mL for BAC, BHC, BMC, ACN). At the same time, CL/F was significantly decreased from 1030.15 to 607.09, 3594.06 to 1437.54, 1441.23 to 1310.14, and 391.30 to 239.50 mL/h for each one after combination. Conclusions: Fuzi diterpene alkaloids pharmacokinetics was greatly influenced by Dahuang which may account for the compatibility mechanism of effect-enhancing and toxicity-reducing. © 2016 Springer International Publishing Switzerland Source

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