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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 C_(18)(3.9 mm×150 mm,5μm)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 0~80.00μg·mL~(-1)内线性良好,空腹与餐后的主要药动学参数如下:ρ_(max)分别为20.50和19.09μg·mL~(-1),AUC_(0-48 h)分别为345.4和336.3μg·h·mL~(-1),t_(max)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。
OBJECTIVE To establish a LC-MS / MS method for the determination of levetiracetam in human plasma and to study the fasting and postprandial pharmacokinetics of levetiracetam sustained-release tablets. Methods Waters Symmetry C_ (18) (3.9 mm × 150 mm, 5 μm) column was used. The mobile phase was acetonitrile-5 mmol·L -1 ammonium acetate solution (containing 0.3% formic acid) V). Two subjects crossed fasting or postprandial single oral levetiracetam sustained-release tablets 1 000 mg. Levetiracetam concentrations were determined by LC-MS / MS. Results The plasma concentrations of levetiracetam were linear within the range of 0.100 0-80.00 μg · mL -1. The main pharmacokinetic parameters of fasting and postprandial plasma concentrations of levetiracetam were as follows: ρ max (max) were 20.50 and 19.09 μg · mL -1 ~ (-1), AUC_ (0-48 h) were 345.4 and 336.3 μg · h · mL -1, respectively, and t max was 4.5 and 7.0 h, respectively. Conclusions This method is simple, specific and sensitive and can be used to study the pharmacokinetics of levetiracetam in plasma samples after fasting and postprandial oral administration of 1 000 mg levetiracetam sustained-release tablets. The high-fat and high-calorie diet has an influence on the pharmacokinetics of levetiracetam sustained release tablets, and the peak time of levetiracetam is prolonged.