HPLC-MS法测定大鼠血浆中艾芬地尔浓度及药代动力学研究  

Determination of ifenprodil in rat plasma by HPLC- MS and pharmacokinetic study

作　　者：万美霞[1] 谢沂宏[2] 徐赛[3] 张开莲[3] 

机构地区：[1]陇东学院,庆阳745000 [2]西藏自治区人民政府驻成都办事处医院,成都610000 [3]泸州医学院,泸州646000

出　　处：《药物分析杂志》2014年第12期2133-2138,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：2013年四川省卫生厅课题酒石酸艾芬地尔抗抑郁作用及其快速起效机制研究(课题编号13027)

摘　　要：目的：建立HPLC-MS法测定大鼠体内艾芬地尔的血药浓度,并研究酒石酸艾芬地尔在健康SD大鼠体内的药代动力学特征。方法：血浆样品碱化后采用乙酸乙酯液-液萃取处理,酮康唑为内标。采用C18色谱柱（5μm,4.6 mm×150mm）,以甲醇-p H 7.20醋酸铵溶液为流动相,梯度洗脱（0-3 min,20%A→90%A,80%B→10%B）,流速0.6 m L·min^-1。质谱检测采用电喷雾（ESI）离子源,正离子模式,采用选择离子检测（SIM）方式检测,检测离子分别为m/z 326.3（艾芬地尔）、m/z 531.0（酮康唑）。选取健康SD大鼠[（250±20）g,雌雄各半],腹腔注射酒石酸艾芬地尔1 mg·kg-1后,采用建立的HPLC-MS法测定各个时间点（0、10、20、30、40、50、60、75、90、100、110、120、150、180、240、360 min,每个时间点6只）大鼠血浆中艾芬地尔的浓度,并计算其药代动力学参数。结果：艾芬地尔浓度在0.5-120μg·L^-1范围内,线性良好（r=0.9974）;日间、日内精密度RSD均小于10.5%,提取回收率均高于88%,专属性良好,血浆样品在本实验的条件下稳定,空白基质中的内源性物质不干扰待测组分和内标的测定。结论：本分析方法对血浆中艾芬地尔的检测具有专属性,且灵敏、可靠。酒石酸艾芬地尔经腹腔注射后在大鼠体内药动学模型为单室模型,其达峰浓度为113.79μg·L^-1,半衰期为2.42 h。Objective： To develop an HPLC - MS method for the determination of ifenprodil in rat plasma and stud- y its pharrnacokinetic characteristics in healthy SD rats. Methods： Liquid - liquid extraction of ifenprodil from plas- ma samples with ethyl acetate was conducted after alkalization by ammonia water. Ketoeonazole was used as the in- ternal standard. The C 18 column （5 μ m,4. 6 mm × 150 mm）was used with the mobile phase of methanol -ammoni- um acetate solution（ pH 7.20 ） and gradient elution（0 - 3 min ,20% A→90% A ,80% B→10% B ） at the flow rate of 0. 6 mL· min^-1. The detection was performed in single ion monitor in positive ionization mode with an electrospray ionization（ESI） source. The single ion monitored were respectively m/z 326. 3 for ifenprodil and m/z 531.0 for ketoconazole. Healthy SD rats [ （250 ± 20 ） g, half male and half female ] received intraperitoneal injection of ifen- prodil tartrate （ 1 mg ·kg-1 ）. The concentration and the pharmacokinetic parameters of ifenprodil were calculated by HPLC - MS for every six healthy rats at each time point （0 min, 10 min, 20 min, 30 min, 40 min, 50 min, 60 rain ,75 min ,90 min, 100 min, 110 min, 120 min, 150 min, 180 rain ,240 min ,360 min） after administration. Re- sults：The assay was linear in the range of 0. 5 - 120 μg · L^-1. The concentrations with a correlation coefficient （r） of 0. 9974. RSDs of the intra - day and inter - day precision tests were lower than 10. 5% and the extraction recov- ery was higher than 88%. The stability of this HPLC - MS method was satisfactory. There was no obvious interference of endogenous substances in black matrix on ion suppression or enhancement phenomenon. Conclusion： The analytical method developed is sensitive,specific,rapid, and reproducible, and it is suitable for the pharmacokinetic study of ifen- prodil in rats. The peak concentration of ifenprodil tartrate in rats is 113.79 μg · L^-1 and the half - life is 2. 42 h. The pharmacokinetic model after intraperitoneal

关 键 词：酒石酸艾芬地尔 血浆样品 血药浓度 液-液萃取 高效液相色谱-质谱法 药代动力学 单室模型 

分 类 号：R917[医药卫生—药物分析学]