目的：建立同时测定人血浆中氯吡格雷（CLO）及其活性代谢产物（CATM）、非活性代谢产物（CCAM）浓度的方法，并用

于药动学研究。方法：取烷化剂2-溴-3′-甲氧基苯乙酮（MPB）保护的血浆样品，经乙腈沉淀蛋白后，以卡马西平为内标，采用超高

效液相色谱-串联质谱（UPLC-MS/MS）法测定。色谱柱为Waters ACQUITY UPLC HSS T3，流动相为水（含0.1％甲酸）-乙腈（含

0.1％甲酸），梯度洗脱，流速为0.50 ml/min。采用电喷雾电离源（ESI），多反应监测（MRM）方式进行正离子监测，用于定量分析的

离子对分别为m/z 322.1→211.8（CLO）、m/z 504.1→155.0（CATM烷化衍生物，CATMD）、m/z 308.3→198.0（CCAM）、m/z 273.2→

194.3（内标）。结果：CLO、CATMD、CCAM血药浓度分别在0.03～20.00、0.30～200.00、10.00～10 000.00 ng/ml 范围内线性关系良

好；日内、日间RSD＜15％，相对误差（RE）为－3.5％～5.7。5 名健康受试者单剂量口服CLO 300 mg后，CLO、CATM、CCAM的

cmax分别为（7.89±5.46）、（15.58±8.08）、（8 023.33±1 047.39）ng/ml，tmax分别为（1.25±0.43）、（1.25±0.43）、（1.67±0.29）h，t1/2分别

为（2.31±0.61）、（0.64±0.08）、（6.53±2.55）h，AUC0-t分别为（17.19±14.59）、（21.39±9.58）、（30 648.85±8 026.63）ng·h/ml。结

论：该方法操作简便、灵敏度高、分析时间短，适用于CLO及其代谢物血药浓度测定及药动学研究。

OBJECTIVE：To establish the method for the simultaneous determination of clopidogrel（CLO）and its active

metabolites（CATM）and inactive metabolites（CCAM），and to conduct pharmacokinetic study. METHODS：The plasma sample

had been derivatized by 2-bromine-3′ -methoxy acetophenone（MPB），and was precipitated by acetonitrile. Using carbamazepine

as internal standard，UPLC-MS/MS was adopted. The separation was performed on Waters ACQUITY UPLC HSS T3

column with mobile phase consisted of water（containing 0.1％ formic acid）-acetonitrile（containing 0.1％ formic acid）using a

gradient elution program at the flow rate of 0.50 ml/min. The ESI was equipped and quantitative analysis was operated in positive

ion and MRM mode. The mass transition ion-pairs were followed as m/z 322.1→211.8（CLO），m/z 504.1→155.0（the alkylation

derivatives of CATM，CATMD），m/z 308.3→198.0（CCAM），m/z 273.2→194.3（internal standard）. RESULTS：The linear

calibration curves for CLO，CATMD and CCAM were obtained in the concentration range of 0.03-20.00 ng/ml，0.30-200.00

ng/ml and 10.00-10 000.00 ng/ml in plasma，respectively；intra-day and inter-day RSD for them were all less than 15％，and

relative error（RE）ranged from －3.5％ to 5.7％. Main pharmacokinetic parameters of CLO，CATMD and CCAM in 5 healthy

volunteers after oral administration of CLO 300 mg were as follows：cmax were（7.89±5.46），（15.58±8.08），（8 023.33±

1 047.39）ng/ml；tmax were（1.25±0.43），（1.25±0.43），（1.67±0.29）h；t1/2 were（2.31±0.61），（0.64±0.08），（6.53±2.55）h；

AUC0-t were（17.19±14.59），（21.39±9.58），（30 648.85±8 026.63）ng·h/ml. CONCLUSIONS：The established method is sensitive，

rapid and convenient，which is suitable for pharmacokinetic study and plasma concentration determination of CLO and its

metabolites.