【摘要】 目的:对紫杉醇纳米脂质体在大鼠体内的药动学进行研究。方法:大鼠尾静脉注射紫杉醇纳米脂质体及紫杉醇注射液,建立液相-质谱联用分析(LC-MS/MS)方法测定血浆中的紫杉醇药物浓度。结果:血药浓度在0.2~1 000μg.L-1范围内线性良好(r=0.999 6),方法回收率及提取回收率均大于90%,日内,日间精密度RSD<15%。紫杉醇纳米脂质体及市售紫杉醇注射液血浓经时曲线均符合二室模型。t1/2α分别为(0.71±0.25)h和(0.438±0.023)h,t1/2β分别为(13.2±1.2)h和(7.8±1.4)h,AUC分别为(4 519.7±791.3)μg.L-1.h和(2 679.2±530.7μg.L-1.h)。结论:本法灵敏度高,准确、可靠。与市售紫杉醇注射液相比,紫杉醇纳米脂质体有一定的长循环作用且可提高在大鼠体内的生物利用度。更多还原

【Abstract】 OBJECTIVE To study the pharmacokinetics of paclitaxel nanoliposome in rats administered i.v.METHODS A LC-MS/MS method based on positive electrospray ionization(ESI⁺-MS-MS) for quantifying paclitaxel in rat blood has been developed.Liquid-liquid extraction with tert-butyl methyl ether was used for plasma sample preparation and docetaxel was used as the internal standard.Paclitaxel nanoliposome and taxol injection were administered through tail vein.RESULTS The standard curve was linear over the concentration range of（0.2）-1 000 μg·L^-1（r=（0.999 6））.The method had a high extraction recovery（>90%） and method recovery（>90%） with intraday and interday precision of <15%.The plasma concentration-time profile in rat after iv injection of paclitaxel nanoliposome or taxol injection followed a bi-exponential disposition.t_1/2α were（（0.71）±（0.25）） h and（（0.438）±（0.023）） h,t_1/2β were（（13.2）±（1.2）） h and（（7.8）±（1.4）） h,AUC were（（4 519.7）±（791.3）） μg·L^-1·h and（（2 679.2）±（530.7）） μg·L^-1·h,respectively.CONCLUSION The LC-MS/MS method bears characteristics of high sensitivity,accuracy and reliability.Paclitaxel nanoliposme has a long-circulating action and improves bioavailabilty of paclitaxle in rat to some extent by comparison with conventional taxol injection.更多还原