目的 建立LC-MS/MS测定人血浆中左乙拉西坦浓度,应用于左乙拉西坦缓释片空腹和餐后药动力学研究。方法 采用Waters Symmetry C18(3.9 mm×150 mm,5 μm)色谱柱,流动相为乙腈-5 mmol·L-1醋酸铵水溶液(含0.3%甲酸)=10∶90(V/V)。2名受试者交叉空腹或餐后单次口服左乙拉西坦缓释片1 000 mg。通过LC-MS/MS测定左乙拉西坦浓度。结果 左乙拉西坦血浆质量浓度在0.100 0~80.00 μg·mL-1内线性良好,空腹与餐后的主要药动学参数如下:ρmax分别为20.50和19.09 μg·mL-1,AUC0-48 h分别为345.4和336.3 μg·h·mL-1,tmax分别为4.5和7.0 h。结论 该方法简便、特异性高、灵敏度高,可用于受试者空腹和餐后口服1 000 mg左乙拉西坦缓释片后血浆样品中左乙拉西坦药动学研究。高脂高热量饮食对左乙拉西坦缓释片的药动学特征有影响,左乙拉西坦的达峰时间延长。
Abstract
OBJECTIVE To establish an LC-MS/MS method for the determination of levetiracetam to investigate the pharmacokinetics of levetiracetam extended-release tablets at fasted and fed states. METHODS The separation was achieved on a Waters Symmetry C18 column (3.9 mm×150 mm,5 μm) with mobile phase consisting of acetonitrile-5 mmol·L-1 ammonium acetate and 0.3% formic acid aqueous solution (10/90, V/V). Two subjects were randomly assigned to receive single oral dose of levetiracetam extended-release tablets 1 000 mg after being fasted and fed by a randomized crossover design. The plasma concentrations of levetiracetam were measured by LC-MS/MS. RESULTS The calibration curve of levetiracetam in human plasma was linear over the concentration rang of 0.100 0-80.00 μg·mL-1. Under fasted and fed conditions, the main pharmacokinetic parameters of levetiracetam were as follows:ρmax were 20.50 and 19.09 μg·mL-1, AUC0-48 h were 345.4 and 336.3 μg·h·mL-1, tmax were 4.5 and 7.0 h, respectively. CONCLUSION The method is proved to be convenient, accurate and sensitive, and suitable for the pharmacokinetic study of 1 000 mg levetiracetam extended-release tablets in healthy Chinese volunteers after being fasted and fed. The result suggests that high fat and calories diet has effect on the pharmacokinetics of levetiracetam extended-release tablets, with tmax being delayed.
关键词
左乙拉西坦 /
缓释片 /
药代动力学 /
高脂高热量饮食 /
高效液相-串联质谱方法 /
食品药物相互作用
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Key words
levetiracetam /
extended-release tablet /
pharmacokinetics /
high fat and calories diet /
LC-MS/MS /
food-drug interaction
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中图分类号：
R969.1
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参考文献
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