气相色谱-质谱联用法测定Beagle犬血清中托吡酯浓度及药动学研究

目的:建立测定犬血清中托吡酯浓度的方法,并用于药动学研究。方法:采用气相色谱-质谱联用法。以盐酸阿米替林为内标,色谱柱为DM-5弹性石英毛细管柱,150～280℃程序升温,选择m/z为202和324的离子碎片峰分别对盐酸阿米替林和托吡酯进行检测。将4只Beagle犬灌胃给予托吡酯(20mg·kg-1),于不同时间点(0.25、0.5、0.75、1、1.5、2、4、6、10、14、20、26、36h)采集血样,计算主要的药动学参数。结果:托吡酯检测浓度线性范围为0.18～35.93mg·L-1(r=0.9994),日内RSD≤8.53%,日间RSD≤14.19%,方法回收率为101.4%,萃取回收率为64.09%;t1/2α为(1.113±0.307)h,t1/2β为(10.209±8.89)h,cmax为(10.96±2.45)mg·L-1,AUC0～∞为(60.317±17.828)mg·h·L-1。结论:所建立的方法灵敏、准确,可用于血清托吡酯浓度的测定及药动学研究。

Determination of Serum Concentration of Topiramate in Beagle Dogs by GC-MS and Its Pharmacokinetic Study

OBJECTIVE：To establish the determination method of serum concentration of topiramate in Beagle dogs and to study its pharmacokinetics.METHODS：A capillary gas chromatogram-mass spectrometry（GC-MS）was adopted with amitriptyline hydrochloride as internal standard.DM-5 capillary column was used with its temperature increasing from 150℃ to 280℃;and the detection was carried out at m/z 202 and 324 by Selective Ion Mode（SIM）to determine amitriptyline hydrochloride and topiramate respectively.4 Beagle dogs received topiramate at dosage of 20 mg·kg -1 by intragastric administration.Blood samples were collected at different time（0.25 h,0.5 h,0.75 h,1 h,1.5 h,2 h,4 h,6 h,10 h,14 h,20 h,26 h,36 h）and pharmacokinetic parameters were calculated.RESULTS：The concentration of topiramate was linear with a range of 0.18～35.93 mg·L -1 （r=0.999 4）.The RSD of intra-day and inter-day were less than 8.53% and 14.19%,the average method recovery and extraction recovery was 101.4% and 64.09% respectively.The main pharmacokinetic parameters were as follows：t 1/2α ：（1.113±0.307）h,t 1/2β ：（10.209± 8.89）h,c max ：（10.96±2.45）mg·L -1 ,AUC 0～∞ ：（60.317±17.828）mg·h·L -1 .CONCLUSION：The method is sensitive and accurate and can be used for concentration determination of topiramate in serum and its pharmacokinetic study.