HPLC-MS/MS法测定大鼠血浆中紫杉醇含量及其脂质体药代动力学研究  

Quantitation of paclitaxel in rats plasma by HPLC-MS/MS and its application in pharmacokinetic study

作　　者：宋妍 SONG Yan(Department of Pharmacy, The Second Hospital,Tianjin Medical University,Tianjin 300211, China)

机构地区：[1]天津医科大学第二医院药学部

出　　处：《天津医科大学学报》2019年第3期292-295,共4页Journal of Tianjin Medical University

摘　　要：目的:建立一种测定大鼠血浆中紫杉醇浓度的高效液相色谱串联质谱(HPLC-MS/MS)分析方法,并研究其脂质体的药代动力学。方法:对6只SD大鼠静脉注射1 mg/kg的紫杉醇脂质体注射液,分别于给药后0、0.5、1、2、4、8、12、24、48 h自眼眶取血0.2 mL,C18反相色谱柱作为固定相,水(1 mmoL/L甲酸铵-0.05%甲酸)-甲醇作为流动相,ESI+扫描模式,MRM监测模式,药代动力学参数采用DAS 2.0软件进行计算。结果:紫杉醇在1~5 000 ng/mL范围内线性较好(R2 =0.999 7),定量下限(LLOQ)为1 ng/mL,日内和日间精密度均低于10%,紫杉醇脂质体给药后血药浓度-时间曲线满足二室模型,主要药代动力学参数t1/2、Cmax、AUC0→t分别为(4.79±0.85)h、(49 785.12±1 618.45)μg/L、(38 753.08±6 144.66)μg/L·h。结论:本方法专属性和灵敏度高,结果可靠,能满足测定大鼠血浆中紫杉醇的定量需求。Objective: To establish a method for the determination of paclitaxel in rat plasma by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS) and to study the pharmacokinetics of paclitaxel liposomes. Methods: Six SD rats were intravenously injected with 1 mg/kg of paclitaxel liposome. The blood samples were taken from the orbit at 0,0.5,1,2,4,8,12,24 and 48 h after administration. The C18 column was used as stationary phase, water (1 mmoL/L ammonium formate-0.05% formic acid)- methanol were chosen as mobile phase, ESI+ scanning mode, and MRM monitoring mode were chosen. The mechanical parameters were calculated by DAS 2.0 software. Results: The linearity of paclitaxel was good in the range of 1~5 000 ng/mL (R2 =0.999 7), the lower limit of quantification (LLOQ) was 1 ng/mL, and the inter-day and intra-day precisions were both less than 10%. The AUC curve of paclitaxel liposomes after administration satisfied the two-compartment model. The main pharmacokinetic parameters t1/2, Cmax and AUC0→t were(4.79±0.85) h,(49 785.12±1 618.45)μg/L, and (38 753.08±6 144.66)μg/L·h, respectively. Conclusion: The method is specific, sensitive and reliable, and may be useful in paclitaxel in rats plasma.

关 键 词：高效液相色谱串联质谱 紫杉醇 药代动力学参数 血浆 

分 类 号：R9[医药卫生—药学]