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目的建立比格犬血浆中知母皂苷B-Ⅱ的LC-MS/MS测定方法,并应用于知母皂苷B-Ⅱ的药代动力学研究。方法液相色谱分离采用ODS柱(150 mm×2.1 mm,5μm),以乙腈-0.05%甲酸溶液(35∶65)为流动相,质谱检测采用ESI离子源,MRM负离子模式。将6只比格犬随机分成2组,单剂量交叉静注或口服知母皂苷B-Ⅱ,剂量分别为2,30 mg.kg-1,定时采集血样,测定比格犬体内的血药浓度,并计算药代动力学参数。结果比格犬静注和口服知母皂苷B-Ⅱ后的主要药代动力学参数如下:Cmax分别为(21507±7307)、(313±149)ng.mL-1;AUC0-t分别为(19177±5692)、(1879±738)ng.h.mL-1;AUC0-∞分别为(19770±5879)、(2153±695)ng.h.mL-1;t1/2分别为(7.81±2.61)、(6.01±5.28)h;MRT0-t分别为(2.89±0.39)、(6.27±1.80)h;MRT0-∞分别为(3.88±0.39)、(8.59±3.18)h。结论该法可用于比格犬血浆中知母皂苷B-Ⅱ的检测及其体内药代动力学研究,比格犬口服知母皂苷B-Ⅱ后的绝对生物利用度为(0.72±0.29)%。
Objective To establish a LC-MS / MS method for the determination of timosaponin B-Ⅱ in plasma of beagle dogs and apply it to the pharmacokinetic study of timosaponin B-Ⅱ. Methods The liquid chromatographic separation was performed on an ODS column (150 mm × 2.1 mm, 5 μm) using acetonitrile-0.05% formic acid solution (35:65) as the mobile phase and ESI ion source and MRM negative ion mode. Six Beagle dogs were randomly divided into 2 groups: single-dose crossover injection or oral administration of timosaponin B-Ⅱ at dosage of 2, 30 mg.kg-1 respectively. The blood samples were collected periodically and the plasma concentration of beagle dogs , And calculated pharmacokinetic parameters. Results The main pharmacokinetic parameters of Beagle dogs after intravenous and oral administration of timosaponin B-Ⅱ were as follows: Cmax were (21507 ± 7307) and (313 ± 149) ng.mL-1 respectively; AUC0- 19177 ± 5692), (1879 ± 738) ng.h.mL-1; AUC0-∞ were (19770 ± 5879) and (2153 ± 695) ng.h.mL- (6.01 ± 5.28) h; MRT0-t were (2.89 ± 0.39) and (6.27 ± 1.80) h respectively; MRT0-∞ were (3.88 ± 0.39) and (8.59 ± 3.18) h respectively. Conclusion The method can be applied to the determination of timosaponin B-Ⅱ in Beagle dog’s plasma and its in vivo pharmacokinetics. The absolute bioavailability of benazepril after oral administration of timosaponin B-Ⅱ was (0.72 ± 0.29)% .