【摘要】：目的:建立測定人血漿中氯吡格雷及其活性和非活性代謝產物濃度的超高效液相色譜-串聯(lián)質譜檢測方法,并將其應用于氯吡格雷在中國健康人群的藥代動力學特征研究。方法:采用液液萃取法和蛋白沉淀法處理血漿樣品,測定原藥、活性代謝產物和非活性代謝產物濃度。液相色譜-質譜條件:采用Thermo C18(100 mm×2.1 mm,5μm)色譜柱,以乙腈(含0.1%甲酸)-水(含0.1%甲酸)(9∶1)為流動相,流速200μL·min-1;正離子模式多反應監(jiān)測掃描分析,離子通道分別為氯吡格雷m/z 321.7→211.9,活性代謝產物m/z 503.6→353.8,非活性代謝產物m/z 307.7→197.8,內標氯雷他定m/z382.8→336.9和卡馬西平m/z 237.1→194.1。11例健康受試者口服300 mg負荷劑量的氯吡格雷,于不同時間點分別采集靜脈血進行藥代動力學分析。結果:血漿中氯吡格雷及其活性和非活性代謝產物線性范圍分別為0.1~20、1~200和25~10 000 ng·m L-1,定量下限分別為0.1、1和25 ng·m L-1,回收率分別在49.2%~53.7%、50.9%~54.3%和95.5%~103.5%之間,批內、批間精密度RSD均小于11%,內標氯雷他定的提取回收率為58.9%,卡馬西平的提取回收率為105.9%。穩(wěn)定性試驗中,在各種貯存條件下氯吡格雷、活性代謝產物、非活性代謝產物均穩(wěn)定性良好。藥動學結果顯示,健康受試者口服300 mg氯吡格雷后,氯吡格雷、活性代謝產物及非活性代謝產物在人體內平均Cmax分別為(3.84±1.26)、(90.75±44.75)和(15 423.31±5 960.89)ng·m L-1,平均tmax分別為(1.02±0.43)、(0.82±0.28)和(0.98±0.31)h,平均t1/2分別為(6.22±4.00)、(0.46±0.12)和(7.16±0.92)h,平均AUC0-∞分別為(12.88±4.72)、(102.47±38.13)和(52 797.00±17 854.92)ng·m L-1·h。結論:該方法操作簡便快速,重復性好,特異性強,靈敏度高,可用于氯吡格雷的藥動學研究。
[Abstract]:Objective: to establish an ultra-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method for the determination of clopidogrel and its active metabolites in human plasma and to study the pharmacokinetics of clopidogrel in healthy Chinese population. Methods: plasma samples were treated by liquid-liquid extraction and protein precipitation method, and the concentrations of raw drugs, active metabolites and non-active metabolites were determined. The conditions of liquid chromatography-mass spectrometry were as follows: Thermo C18 (100 mm 脳 2.1 mm, 5 渭 m) column was used, the mobile phase was acetonitrile (containing 0.1% formic acid)-water (containing 0.1% formic acid) (9:1), and the flow rate was 200 渭 L 路min-1. Positive ion mode multi-reaction scanning analysis showed that the ion channels were clopidogrel m 鈮，

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