大鼠血浆中积雪草总苷多成分的LC-MS法测定及其药动学  

Determination of Multi-constituents of Centella Total Glucosides by LC-MS in Rat Plasma and Their Pharmacokinetics

作　　者：欧阳丹薇[1] 肖峰[1] 秦燕[1] 邵燕[1] 孔德云[1] 

机构地区：[1]中国医药工业研究总院上海医药工业研究院,创新药物与制药工艺国家重点实验室,上海200040

出　　处：《中国医药工业杂志》2014年第5期460-466,共7页Chinese Journal of Pharmaceuticals

基　　金：上海市自然科学基金项目(11ZR1435300)

摘　　要：建立了液相色谱-质谱法测定大鼠血浆中积雪草总苷中的多种三萜皂苷类成分,并考察积雪草总苷静注和口服给药后在大鼠体内的药动学。选用Kromasil C18色谱柱,以0.1%甲酸(含10 mmol/L甲酸铵)︰甲醇为流动相,梯度洗脱;采用电喷雾离子源(ESI源),多反应监测(MRM),正离子检测,使用DAS 2.0软件的非房室模型计算药动学参数。大鼠静注给予5 mg/kg积雪草总苷后,积雪草苷、羟基积雪草苷+积雪草苷B、积雪草酸和羟基积雪草酸的主要药动学参数如下:t1/2分别为(1.65±0.80)、(3.02±0.55)、(3.75±1.93)和(0.31±0.08)h;cmax分别为(2 622±555)、(23 800±2 138)、(483±128)和(605±124)ng/ml;AUC0→t分别为(572±125)、(7 703±639)、(185±32)和(100±22)ng·h·ml-1;AUC0→Cmax分别为(581±127)、(7 722±639)、(206±37)和(101±22)ng·h·ml-1。口服给予150 mg/kg积雪草总苷后,羟基积雪草苷+积雪草苷B和积雪草酸的的主要药动学参数如下:t1/2为(3.41±1.27)和(5.25±2.50)h,cmax为(97.6±38.2)和(42.3±14.0)ng/ml,AUC0→t为(435±38)和(377±52)ng·h·ml-1,AUC0→t为(446±38)和(427±72)ng·h·ml-1。口服给药后,羟基积雪草苷+积雪草苷B、积雪草酸的药-时曲线均出现双峰,提示可能存在肝肠循环。积雪草总苷口服给药的绝对生物利用度为(0.081±0.011)%。An LC-MS method was established for the determination of the triterpenoid saponins in Centella total glucosides （CTG） in rat plasma and the pharmacokinetic properties of CTG in rats were studied after oral and intravenous administrations. A Kromasil C18 column was used with the mobile phase of 0.1% formic acid solution （containing 10 mmol/L ammonium formate） ： methanol by gradient elution. A mass spectrometry was applied with ESI ion source in the positive ion multiple reaction monitoring （MRM） mode. All pharmacokinetic parameters were processed by non- compartmental analysis with DAS 2.0 software. After CTG was intravenously administered at 5 mg/kg dose, the main pharmacokinetic parameters of asiaticoside, madecassoside＋asiaticoside B, asiatic acid and madecassic acid were as follows： t1/2 （1.65±0.80）, （3.02±0.55）, （3.75±1.93） and （0.31±0.08）h; Cmax （2 622±555）, （23 800±2 138）, （483± 128） and （605±124）ng/ml; AUC0-t（572±125）, （7 703±639）, （185±32） and （100±22）ng.h.ml ^-1; AUC0→∞（581±127）, （7 722±639）, （206±37） and （101＋22）ng.h-ml 1. While after CTG was orally administered at 150 mg/kg dose, the main pharmacokinetic parameters of madecassoside＋asiaticoside B and asiatic acid were as follows： t1/2 （3.41±1.27） and （5.25±2.50）h, Cmax （97.6±38.2） and （42.3±14.0）ng/ml, AUC0-t（435±38） and （377±52）ng·h·ml^-1, AUC0→∞（446± 38） and （427±72）ng-h·ml-1. The concentration-time profiles of madecassoside＋asiaticoside B and asiatic acid showed double-peak phenomenon after oral administration, inferring that there might be a hepato-enteral circulation. The absolute bioavailability of CTG was （0.081 ±0.011 ） %.

关 键 词：积雪草总苷 三萜皂苷类 液相色谱-质谱 药动学 

分 类 号：O657.79[理学—分析化学] R969[理学—化学]