摘要
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 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 spectrom- etry 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-L of tim- osaponin 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 ad- ministration were as follows： Cmax being（21507±7307） ng＇mLI vs （313±149） ng·mL-1, AUC0-1 being（19177±5692） ng·h·mL-1 vs （1879±738） ng.h.mL-1, AUC0-1 being（19770±5879） ng.h-mL-1 vs （2153_695） ng-h.mL-1, tl8 being （7.81＋_2.61） h vs （6.01±5.28） h, MRT0_, being（2.89±0.39） h vs （6.27±1.80） h, and MRT0-1 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-I1 and assess the pharmacokinetics in beagle dogs, with the absolute bioavailability being（0.72±0.29） % after oral adminstration.
出处
《中药新药与临床药理》
CAS
CSCD
北大核心
2013年第1期66-70,共5页
Traditional Chinese Drug Research and Clinical Pharmacology
