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篇名: | UPLC-MS/MS法同时测定人血浆中氯吡格雷及其代谢物的浓度 |
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摘要: | 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。 |
ABSTRACT: | 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. |
期刊: | 2015年第26卷第35期 |
作者: | 孙增先,王海东,倪善红,程聪,刘乃丰 |
AUTHORS: | SUN Zeng-xian,WANG Hai-dong,NI Shan-hong,CHENG Cong,LIU Nai-feng |
关键字: | 氯吡格雷;活性代谢产物;非活性代谢产物;超高效液相色谱-串联质谱法;血药浓度;药动学 |
KEYWORDS: | Clopidogrel;Active metabolite;Inactive metabolite;UPLC-MS/MS;Plasma concentration;Pharmacokinetcs |
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