摘要
目的建立-种液相色谱-串联质谱(LC—MS/MS)的方法,测定人血浆中紫杉醇的药物浓度。方法色谱柱:DiamonsilC18柱(50mm×2.1mm.D,粒径5岬,北京迪马公司),流动相:乙腈-水-甲酸(体积比为55.0:45.0:0.1),采用沉淀蛋白法,以多反应离子监测(multiplereactionmoni·toring,MRM)扫描方式进行检测,测定肿瘤患者静脉滴注紫杉醇注射液后血浆中的药物浓度。结果血浆中紫杉醇的药物浓度在20.0—5000.0pLg·L-1以内时,其线性关系良好,相关系数r=0.9954;日内和日间精密度RSD≤13.4%;紫杉醇的平均提取回收率为93.6%-108.5%,紫杉醇的基质效应为102.4%~105.4%,紫杉醇在人血浆中主要药动学参数如下:为(5.1±3.0)h,pm“为(3.8±O.5)mg·L-1,AUC06为(13.2±2.6)mg·h·L-1,AUC0为(13.34-2.8)mg·h·L-1。结论该方法适用于紫杉醇在人体内的药物动力学研究。
Objective To develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS)method for the determination of paclitaxel in human plasma. Methods The chromatographic separation was accom plished on Diamonsil C18 analytical column( 50 mm x 2. 1 mm I. D ,5 μm, Dikma)with the mobile phase consisting of acetonitrile: water: formic acid ( V: V: V = 55, 0: 45.0: 0. 1 ). Protein precipitation was used for the sample pretreatment. The plasma concentration was detected by multiple reactions monitoring after the cancer patients were given paclitaxel. Results The method was linear over the range of 20. 0-5 000. 0 Ixg'L- 1, r =0. 995 4 ;The intra-and inter-day precisions were less than 13.4%. The average recoveries were between 93.6% and 108.5%. The matrix effects were between 102.4% and 105.4%. The main pharmacokinetic pa- rameters were as follows: t1/2 ( 5. 1±3.0 ) h, Pmax ( 3. 8±0. 5 ) mg. L -1, AUC0.36 ( 13.2 ±2. 6 ) mg. h. L - 1, AUC0. (13.3± 2.8)mg. h. L-1, respectively. Conclusions This method was applied to pharmacokinetic studies of paclitaxel in human plasma.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2013年第10期776-781,787,共7页
Journal of Shenyang Pharmaceutical University