HPLC-MS/MS法测定达卡巴嗪脂质体的血药浓度

Determination the concentration of dacarbazinelipidosome in plasma by HPLC-MS/MS

目的建立高效液相色谱-质谱联用法(HPLC-MS/MS)测定血浆中达卡巴嗪(DTIC)的浓度。方法以电喷雾离子源(ESI)正离子模式,甲硝唑(MTZ)为内标定量,达卡巴嗪检测离子对为m/z 183.2→m/z 166.1;甲硝唑检测离子对为m/z 172.1→m/z 128.1,乙腈沉淀蛋白处理,用Dikmatech Easy GuardⅡHolder Assem Lly保护柱,Dikmatech C18(2.1 mm×50 mm,3μm)分析柱分离样品,流动相:水(含10 mmol·L^(-1)乙酸铵,0.1%乙酸,用氨水调p H至6.0)-乙腈=94∶6(v∶v);流速:0.3 m L·min^(-1)。结果达卡巴嗪标准曲线方程为Y=0.106X+0.0969(R=0.998 8),在0.5~20μg·m L^(-1)线性关系良好,定量下限为0.5μg·m L^(-1),达卡巴嗪日内和日间精密度的相对标准偏差为1.30%~3.00%和2.19%~8.78%。结论本文建立的方法灵敏可靠,可用于测定血浆中达卡巴嗪脂质体的浓度。

Objective To establish a HPLC-MS/MS method to determinate dacarbazine concentrations in rat plasma. Methods The mass spectrometer was operated in positive electron spray lonization（ ESI）model and used metronidazole as internal standard,m/z 183. 2 → m/z166. 1 and m/z 172. 1→m/z 128. 1 were used for the measurement of dacarbazine and metronidazole,respectively. The plasma was deproteinated by acetonitrile and separated by a Dikmatech Easy Guard Holder Assembly guard column and a Dikmatech C18（ 2. 1 mm × 50 mm,3 μm） column with a mobile phase of water-acetonitrile solution（ containing 10 mmol·L^（-1） ammonium acetate,p H6. 0,94 ∶ 6,v/v） at the flow rate of0. 3 m L·min^（-1）. Results The linear range of dacarbazine was 0. 5-20μg·m L^（-1）. The inter-day and intra-day precision relative standard deviation（ RSD） of dacarbazine in plasma were 1. 30%-3. 00% and2. 19%-8. 78%. Conclusion The HPLC-MS/MS developed in this study is rapid,accurate and reliable,and was accurate for determination of dacarbazinelipidosome in rat plasma.