液相色谱-串联质谱法测定乳腺癌患者人血浆中伊沙匹隆浓度及其药代动力学研究

目的 建立液相色谱-串联质谱联用方法测定人血浆中伊沙匹隆(抗肿瘤药)浓度,并研究其在乳腺癌患者中的药代动力学.方法 用BDS Hypersil C_(18)色谱柱(100 mm ×2.1 mm,3μm),流动相为0.01 mol·L~(-1)乙酸胺-乙腈=40:60,样本经质谱ESI源正离子化后,用多反应离子监测方式对伊沙匹隆进行测定.结果 血浆中伊沙匹隆在2～500 ng·mL~(-1)线性良好;提取回收率为61.85%～65.85%,批内、批间精密度良好(RSD<5%).11例乳腺癌患者的主要药代动力学参数:C_(max)为(295.34±140.74)ng·mL~(-1),t_(1/2)为(41.77±19.05)h,AUC_(0-∞)为(2.80±1.66)μg·h·mL~(-1),V_(ss)为(1267.20±419.96)L,CL为(36.72±33.00)L·h~(-1).结论 本方法准确、快速、简单,适用于血浆中伊沙匹隆浓度测定.伊沙匹隆在中国乳腺癌患者中的药代动力学行为与国外患者相似.

Dermination of ixabepilone concerntration and its pharmacokinetics in breast cancer patients by LC-MS/MS

Objective To establish LC-MS/MS method for the deter-mination of ixabepilone in breast cancer patients and evaluate its pharma-cokinetics profile. Methods A BDS Hypersil C_(18) (100 mm ×2. 1 mm,3 μm) column was used with the mobile phase of 0. 01 mol ·L~(-1) ammoni-um acetate-acetonitrile = 40: 60. The concentration was detected by ESI -MS. Results A good linear relationship was obtained in the concen-tration from 2 to 500 ng·mL~(-1). The average recovery of this method was 61.85%-65.85%. Inter-batch RSD and intra-batch RSD were both less than 5 %. The pharmacokinetic parameters of ixabepilone were as follows:C_(max) was (295.34±140.74) ng· mL~(-1),t_(1/2) was (41.77 ± 19. 05) h, AUC_(0-∞) was (2.80 ± 1.66) μg· h· mL~(-1), V_(ss) was (1267.20 ±419.96) L and CL was (36.72 ±33.00) L· h~(-1) ,respec-tively, Condusion The method is simple, rapid and accurate. The method was suitable for the quantitatve determination of ixabepilone. The datas of pharmaeokinetic parameters in Chinese breast cancer patiens is similar to other studies in USA.