LC-MS/MS法同时测定人血浆中阿司匹林和水杨酸的质量浓度

Simultaneous determination of aspirin and salicylic acid in human plasma by LC-MS/MS

目的 建立LC-MS/MS法同时测定人血浆中阿司匹林及其代谢物水杨酸的浓度,并将此方法应用于健康受试者口服阿司匹林肠溶片(100 mg)后的药代动力学研究。方法 健康受试者口服100 mg阿司匹林肠溶片,血浆样品以氟化钾作为稳定剂,经蛋白沉淀法处理后采用LC-MS/MS法检测阿司匹林和水杨酸浓度。使用WinNonlin 6.4计算主要药动学参数。结果 阿司匹林质量浓度在10.0~1 000μg·L~(-1)内线性关系良好,水杨酸质量浓度在100~10 000μg·L~(-1)内线性关系良好,定量下限分别为10.0μg·L~(-1)和100μg·L~(-1)。阿司匹林和水杨酸在试验操作条件下稳定性良好。健康受试者口服100 mg阿司匹林肠溶片后,检测到阿司匹林和水杨酸的ρ_(max)分别为535.77μg·L~(-1)和4 883.17μg·L~(-1),t_(max)分别为4.50 h和5.50 h,t_(1/2)分别为0.55 h和2.40 h。结论 该方法可同时测定人血浆中阿司匹林和水杨酸的浓度,适用于阿司匹林肠溶片在人体内的药物动力学研究。

Objective To establish an LC-MS/MS method for the determination of aspirin and its metabolite salicylic acid in human plasma,and apply this method to the pharmacokinetic study of aspirin and salicylic acid in healthy subjects after taking aspirin enteric-coated tablets(100 mg)orally.Methods Six healthy subjects were given 100 mg of aspirin enteric-coated tablets.Potassium fluoride was used as a stabilizer during blood collection.Plasma samples were treated by protein precipitation and detected by LC-MS/MS method.WinNonlin 6.4 was used to calculate the main pharmacokinetic parameters.Results The standard curves found to be linear in the range of 10.0-1000μg·L-1 and 100-10000μg·L-1 for aspirin and salicylic acid,respectively.Aspirin and salicylic acid were found to be stable during plasma separation and preparation.After adminstration of aspirin enteric-coated tablets,theρmax values of aspirin and salicylic acid were 535.77μg·L-1 and 4883.17μg·L-1;t max values were 4.50 h and 5.50 h,and t 1/2 values were 0.55 h and 2.40 h,respectively.Conclusion An LC-MS/MS method for simultaneous determination of aspirin and salicylic acid in human plasma is established.The validated method has been successfully applied to a pharmacokinetic study following oral administration of aspirin enteric-coated tablets to human volunteers.