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 ）.
出处
《沈阳药科大学学报》
CAS
CSCD
北大核心
2016年第9期741-747,共7页
Journal of Shenyang Pharmaceutical University
