液相色谱-串联质谱法测定全脑缺血损伤模型大鼠体内拉莫三嗪血药浓度及药动学研究

Study on plasma concentration and pharmacoknetics of lamotrigine in cerebral ischemia model rats by LC-MS/MS

目的建立液相色谱-串联质谱法(LC-MS/MS)测定大鼠血浆样品中拉莫三嗪浓度的方法,并进行药动学研究。方法取12只SD大鼠,假手术组、脑缺血损伤模型组各6只,拉莫三嗪10mg/kg灌胃,分别于5min,0.25、0.5、1、2、4、6、8、12、24、36h眼眶隐静脉丛取血,采用LC-MS/MS法测定其血药浓度,并用DAS软件计算药动学参数。结果拉莫三嗪的药动学参数属于一级动力学两房室模型,拉莫三嗪在假手术大鼠体内的药动学参数cmax(1382.87±61.17)μg/L,t1/2(40.43±6.77)h,AUC0-∞(123.45±70.70)mg·h/L。全脑缺血损伤模型大鼠中药动学参数cmax (1 713.50±65.11)μg/L,t1/2(73.72±17.46)h,AUC0-∞(188.15±76.37)mg·h/L。结论本方法适用于大鼠血浆中拉莫三嗪浓度的测定。假手术组和模型组大鼠拉莫三嗪灌胃后均于2h达到峰值,但模型组拉莫三嗪的t1/2较长,血药浓度较高,可为后期药效学研究提供依据。

Objective To establish a sensitive method for determination of concentration of lamotrigine（LTG）in rat plasma and to study the pharmacokinetics by LC-MS/MS.Methods 12 rats were divided evenly into model group and shameoperated group.LTG was given as single dose of 10 mg/kg viaintragastrical administration.Blood samples were collected from orbital saphenous venous plexus at 5 min,0.25,0.5,1,2,4,6,8,12,24 and 36 hafter dosing.The LTG concentrations in rat plasma were assayed by LC-MS/MS.The pharmacokinetic parameters were calculated by DAS software.Results In shameoperated group,cmax（1 382.87±61.17）μg/L,t1/2（40.43±6.77）h;AUC0-∞（123.45±70.70）mg·h/L.In model group,cmax（1 713.50±65.11）μg/L,t1/2（73.72±17.46）h,AUC0-∞（188.15±76.37）mg·h/L.Conclusion The method is proved to be suitable for the determination of LTG in rat plasma.LTG concentration reached peak value at 2 hin both groups.However,model group had a longer t1/2 and higher concentration than that in shame-operated group,which is a valuable information for further pharmacodynamics study.