UPLC-MS/MS法测定大鼠血浆中间氯苯基哌嗪的质量浓度及其在药动学研究中的应用  

UPLC-MS/MS method for determination of mchlorophenylpiperazine in rat plasma and its application to a pharmacokinetic study

作　　者：李欣蕾[1] 隋婷婷[1] 黄秀英[1] 孙璐[1] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2016年第9期741-747,共7页Journal of Shenyang Pharmaceutical University

摘　　要：目的 建立测定大鼠血浆中间氯苯基哌嗪（m-chlorophenylpiperazine,m-CPP）的UPLC-MS/MS方法,并应用该法比较了按m-CPP计相同剂量下,大鼠灌胃给予盐酸WS和盐酸曲唑酮后,m-CPP在大鼠体内的药物动力学行为。方法 色谱柱为Thermo Hypersi L GOLD a Q C18柱（100 mm×2.1mm,1.9μm）,流动相为乙腈-体积分数0.1%甲酸水溶液梯度洗脱,采用乙腈沉淀蛋白法处理血浆样品,以正离子扫描多反应监测模式进行检测。结果 大鼠血浆中的m-CPP在质量浓度为0.20~152.10μg·L-1内线性关系良好（r=0.998 4）,定量下限为0.20μg·L-1,提取回收率大于85%,日内和日间精密度均小于7%,准确度为100.8%~103.5%。20只Sprague Dawley大鼠分别灌胃给予盐酸曲唑酮9.9 mg·kg-1（按m-CPP计4.8 mg·kg-1）和盐酸WS 10.2 mg·kg-1（按m-CPP计4.8mg·kg-1）生理盐水溶液,血浆中m-CPP的tmax分别为（0.6±0.3）和（0.6±0.2）h,ρmax分别为（32.6±16.2）和（22.3±12.0）μg·L-1,AUC0-10分别为（89.0±27.5）和（66.3±17.1）μg·h·L-1,AUC0-∞分别为（96.8±26.8）和（75.3±15.5）μg·h·L-1,t1/2分别为（3.1±1.6）和（4.0±3.9）h。结论 盐酸WS组中m-CPP的AUC0-10和AUC0-∞均大于盐酸曲唑酮组（P〈0.05）,Cl小于盐酸曲唑酮组（P〈0.05）,其他药动学参数无显著性差异（P〉0.05）。Objective To develop a rapid, simple, and specific ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS）method for evaluating the pharmacokinetic behavior of m- chlorophenylpiperazine （m-CPP）in rat. Methods Chromatographic separation was achieved in a run time of 3.5 min on a Thermo Hypesil Gold aQ C18 column（ 100 mm × 2. 1 mm, 1.9 μm） under acetonitrile - 0.1% formic acid gradient conditions. The analytes and the internal standard m-bromophenylpiperazine （m-BPP） were extracted from 50 μL aliquots of rat plasma by protein precipitation with acetonitrile. Results The calibration curve was linear in the range of 0. 20 - 152. 10μg·L -1 （ r = 0. 998 4 ）, and the lower limit of quantification（LLOQ） of the method was 0. 20 μg.L-1. Intra- and inter-day precisions for all samples were less than 7% and the accuracy of three different concentrations was in the range of 100. 8% - 103.5%. The extraction recovery of m-CPP from rat plasma was over 85 %. The main pharmacokinetic parameters of m- CPP after single oral administration of WS hydrochloride and trazodone hydrochloride to rats were shown as follows： tmax,（0.6 ±0.3）and（0.6 ± 0.2）h;pmax,（32.6 ± 16.2）and（22.3 ± 12.0）μg·L-1 t1/2, （3.1 ± 1.6）and（4.0 ± 3.9）h;AUCo.t0,（89.0 ± 27.5）and（66.3 ±17.1）μg·h·L-1;AUC0-∞, （96. 8 ± 26. 8 ）and （75.3 ± 15.5 ） μg· h·L-1, respectively. Conclusions The pharmacokinetic parameters of m-CPP between the two groups showed no significant difference （ P 〉 0.05 ） except that AUC0-10 and AUC0-∞ of WS hydrochloride group were greater than trazodone hydrochloride group （ P 〈 0.05 ）, and clearance of WS hydrochloride group were lower than trazodone hydrochloride group （ P 〈 0.05 ）.

关 键 词：间氯苯基哌嗪 超高效液相-质谱联用法 大鼠 血浆 药物动力学 前药 抗抑郁 5-羟色胺 

分 类 号：R917[医药卫生—药物分析学]