气相色谱-串联质谱法测定犬血清中左羟丙哌嗪浓度及其药动学

Determination of Levodropropizine in Beagle Serum by GC-MS and Its Pharmacokinetic Studies

目的 建立测定左羟丙哌嗪血药浓度的气相色谱-串联质谱联用分析方法,并研究其在犬体内的药动学.方法 采用拉丁方设计,对6只犬均给予3种剂量的左羟丙哌嗪溶液,给药后采集一系列血样,用气相色谱-串联质谱法测定其血药浓度,用3P97药动学程序处理血药浓度数据并计算参数.结果 该法在0.005～4.0 mg·L^-1内线性关系良好（r=0.997 8）,最低检测浓度0.005 mg·L^-1,平均萃取回收率为84.4%～95.4%.日内、日间相对标准差（RSD）均低于5%.6只犬药-时曲线符合一室开放模型,左羟丙哌嗪在犬体内吸收和消除迅速,分布广泛.3种剂量的参数AUC0～∞,ρmax,tmax,t1/2Ka,t1/2Ke,MRT,CL,Vd在个体间、实验周期间均无显著差异（P＞0.05）.结论 建立了左羟丙哌嗪GC-MS血药浓度测定方法.该法专属性强,灵敏度高,适用于左羟丙哌嗪的药动学研究.

OBJECTIVE To establish an analytical method for the determination of levodropropizine in serum and to study its pharmacokinetic profile in dogs.METHODS Six dogs were treated with levodropropizine in three doses. Blood sample were collected after the administration. An analytical method based on Gas chromatographic-mass spectrometry （GS-MS） was established to determine the serum concentration of levodropropizine. Pharmacokinetic evaluation was carried out using the 3197 program. RESULTS The calibration curves were linear over the concentration range of 0. 005 - 4.0 mg·L^-1. The intra-day and inter-day precisions were very good （ 〈 5 % ） at low, medium and high concentrations. The overall recovery of the analytics was 84.4% - 95.4%. Phannacokinetic studies showed that an open one-compartment model best described the concentration-time profiles for levodropropizine.levodropropizine was absorbed rapidly, distributed widely and eliminated quickly in beagle. There were no significant difference in AUC0～∞,ρmax,tmax,t1/2Ka,t1/2Ke,MRT, CL and Vd of the three doses among individuals and experiment cycles. CONCLUSION The analytical method is shown to be sensitive, specific, rapid and reproducible, and is suitable for the pharmacokinetic study of levodropropizine.