Study on plasma concentration and pharmacoknetics of lamotrigine in cerebral ischemia model rats by LC-MS/MS
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摘要: 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10 mg/kg灌胃，分别于5 min，0.25、0.5、1、2、4、6、8、12、24、36 h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2 h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。
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关键词:
- 拉莫三嗪 /
- 液相色谱-串联质谱法 /
- 大鼠血浆 /
- 药动学
Abstract: 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 shame-operated group. LTG was given as single dose of 10 mg/kg via intragastrical 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 h after dosing. The LTG concentrations in rat plasma were assayed by LC-MS/MS. The pharmacokinetic parameters were calculated by DAS software. Results In shame-operated 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 h in 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.-
Key words:
- lamotrigine(LTG) /
- LC-MS/MS /
- rat plasma /
- pharmacokinetic
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