HPLC-MS/MS法测定恒河猴血浆中地尔硫卓的质量浓度  

Determination of diltiazem in rhesus monkey plasma by HPLC-MS /MS

作　　者：付晓菲[1,2] 赵文军[1] 高锦[3] 

机构地区：[1]沈阳军区联勤部药品仪器检验所,辽宁沈阳110026 [2]解放军总医院药品保障中心,北京100853 [3]总后勤部卫生部药品仪器检验所,北京100071

出　　处：《沈阳药科大学学报》2014年第6期483-487,共5页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立恒河猴血浆中地尔硫卓质量浓度的HPLC-MS/MS测定方法。方法采用Agilent Zorbax SB-C18色谱柱（2.1 mm×100 mm,3.5μm）,以乙腈-10 mmol·L^-1醋酸铵（体积比75∶25）为流动相,流速为0.3 mL·min-1,柱温30℃。血浆样品采用叔丁基甲醚沉淀蛋白法处理,质谱采用电喷雾离子源,正离子化检测,扫描方式为多离子反应监测（MRM）。结果地尔硫卓的线性范围为0.2~200.0μg·L^-1,r=0.995 8,日内、日间精密度RSD〈15%,平均提取回收率为70.5%~74.0%,基质效应符合相关规定。地尔硫卓在恒河猴体内主要药代动力学参数：t1/2为（4.06±0.64）h,ρmax为（95.68±13.39）μg·L^-1,AUC0-t为（746.09±45.14）μg·h·L^-1。结论该方法适用于地尔硫卓在恒河猴体内的血药质量浓度检测及药代动力学研究。Objective To develop a high performance liquid chromatography tandem mass spectrometry （HPLC-MS/MS） method for the determination of diltiazem in rhesus monkey plasma. Methods The plasma samples were deproteinated with MTBE, and chromatographic separation was performed on an Agilent Zorb- ax SB-C18 column （2. 1 mm × 100 mm,3.5 μm）. The mobile phase consisted of acetonitrile- 10 mmol.L^-1 CH3COONH4 （ V： V = 75：25 ）at a flow rate of 0. 3 mL. min^- 1 and the column temperature was 30 ℃. A trip- quadrupole tandem mass spectrum with the electrospray ionization （ESI） source was applied and positive ion multiple reaction monitoring mode was operated. Results The method was linear over the range of 0. 2 - 200. 0 μg.L^-1 r =0. 995 8. The intra- and inter-day precision was within 15% in terms of relative standard deviation （RSD%）. The average recoveries were between 70.5% -74.0% ,the matrix effects were up to the specification. Main pharmacokinetics parameters were as follows： t1/2 was （4. 06 ± 0.64） h,ρmax was （95.68 ± 13.39） μg.L^-1 ,AUC0-t was （746.09 ±45.14） μg.h.L^-1. Conclusions This simple and sensitive HPLC-MS/MS method is successfully applied to pharmacokinetic studies of diltiazem in rhesus monkeys.

关 键 词：地尔硫卓 高效液相色谱-串联质谱 恒河猴 药代动力学 

分 类 号：R917[医药卫生—药物分析学]