气-质联用法测定血浆中阿斯匹林和水杨酸浓度及人体药代动力学研究

目的：建立人血浆中阿斯匹林和水杨酸气相色谱-质谱联用测定法，并研究了肠溶阿斯匹林片在健康人体内的药代动力学。方法：色谱柱HP-5 25 m×0.2 mm ID石英弹性毛细管柱。内标苯甲酸，血样酸化后经乙醚—二氯甲烷(4∶1)提取,BSTFA衍生化进样,采用选择离子方式检测、定量。结果：阿斯匹林、水杨酸的日内及日间的RSD分别小于4.78%及6.16%。平均回收率大于96.9%。最小检测浓度:阿斯匹林1.0 ng.mL^-1，水杨酸0.1 μg.mL^-1。8名健康志愿者口服单剂量50 mg肠溶阿斯匹林片后，以本法测定阿斯匹林、水杨酸体内过程符合一室模型。结论：本法用于同时测定阿斯匹林和水杨酸体内浓度，灵敏度高，数据准确可靠。

DETERMINATION OF ASPIRIN AND SALICYLIC ACID IN PLASMA BY GC-MS AND PHARMACOKINETIC STUDIES

AIM: To develop a GC-MS method for the study of pharmacokinetics of aspirin and salicylic acid in healthy human volunteers. METHODS: A 25 m×0.2 mm ID capillary column was used. The carrier gas was helium. Benzene carbonic acid was used as internal standard. The plasma was extracted with ether—dichloromethane (4∶1) after adding 3 mol.L-1 HCl and then reacted with bis-(trimethylsilyl) trifluoroacetamide (BSTFA). The concentrations of aspirin and salicylic acid were measured by GC-MS (SIM). The pharmacokinetic parameters were computed using 3P87 program. RESULTS: A good linearity was obtained from 2.0～400 ng.mL^-1 of aspirin and 0.2～10.0 μg.mL^-1 of salicylic acid in human plasma. The detection limit of aspirin and salicylic acid were 1.0 ng.mL^-1 and 0.1 μg.mL^-1 in plasma, respectively. The results showed that the plasma concentration-time courses conformed to one compartment model following a single oral dose of 50 mg aspirin tablets given to each of the 8 volunteers. CONCLUSION: The established GC-MS method was a good method for determination of aspirin and salicylic acid in human plasma. The method was simple, precise and sensitive.