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，5 μm)，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 develop a LC-MS/MS method for the determination of timosaponin B-II and to apply for its pharmacokinetic study. Methods The analytes were separated on an ODS column(150 mm×2.1 mm，5 μm) with the mobile phase of acetonitrile-0.05 % formic acid(35 ∶ 65) and detected by electrospray ionization mass spectrometry in the negative multiple reaction monitoring(MRM) mode. Six beagle dogs were randomized into two groups by crossover design. The animals were given intravenous administration of 2 mg·kg-1 or oral use of 30 mg·kg-1 of timosaponin B-II，respectively. The concentration of timosaponin B-II was determined after collection of the dog plasma，and then the main pharmacokinetic parameters were calculated. Results The parameters in intravenous vs oral administration were as follows:Cmax being(21507±7307) ng·mL-1 vs (313±149) ng·mL-1，AUC0-t being(19177±5692)ng·h·mL-1 vs (1879±738) ng·h·mL-1，AUC0-∞ being(19770±5879) ng·h·mL-1 vs (2153±695) ng·h·mL-1，t1/2 being(7.81±2.61) h vs (6.01±5.28) h，MRT0-t being(2.89±0.39) h vs (6.27±1.80) h，and MRT0-∞ being(3.88±0.39) h vs (8.59±3.18) h. Conclusion The method has been successfully applied to determine the concentration of timosaponin B-II and assess the pharmacokinetics in beagle dogs，with the absolute bioavailability being(0.72±0.29) % after oral adminstration.

R285.5