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本试验建立了一种简单快速灵敏的液质联用方法, 用以同时测定裸鼠血浆内埃罗替尼及其活性代谢物OSI-420的浓度。采用液液萃取法从血浆中提取埃罗替尼, OSI-420和内标普萘洛, 用C18反相柱进行分离, 流动相为乙腈-5 mM甲酸铵 (35:65, v/v, pH = 3.0)。所有化合物均采用电喷雾电离源, 正离子方式检测。埃罗替尼和OSI-420的最低定量下限均为0.5 ng/mL。埃罗替尼的准确度在0.07%-8.00%范围内, OSI-420准确度在-2.83%-6.67%范围内; 埃罗替尼精密度在2.28%-15.12%范围内, OSI-420精密度在1.96%-11.50%范围内。此方法应用于BALB/c裸鼠口服12.5 mg/kg埃罗替尼的药代动力学研究中, 并用二室模型拟合埃罗替尼的药代动力学, 一室模型拟合OSI-420的药代动力学。代谢为OSI-420的埃罗替尼占埃罗替尼总量的10%, 比文献中的这一比值大一倍, 表明种属间埃罗替尼的代谢存在差异。
In this study, we established a simple, rapid and sensitive LC-MS method for the simultaneous determination of erlotinib and its active metabolite OSI-420 in nude mice plasma. Erlotinib, OSI-420 and internal standard ponzuol were extracted from plasma by liquid-liquid extraction and separated by C18 reverse phase column with acetonitrile-5 mM ammonium formate (35:65, v / v, pH = 3.0). All compounds are electrospray ionization source, positive ion detection. The minimum limit of quantification for both erlotinib and OSI-420 was 0.5 ng / mL. The accuracy of erlotinib was in the range of 0.07% -8.00%, the accuracy of OSI-420 was in the range of -2.83% -6.67%, the precision of erlotinib was in the range of 2.28% -15.12%, and the precision of OSI-420 Degree in the range of 1.96% -11.50%. This method was applied to the pharmacokinetic study of erlotinib at 12.5 mg / kg in BALB / c nude mice. The pharmacokinetics of erlotinib was fitted by two-compartment model and the OSI-420 Pharmacokinetics. Erlotinib metabolized to OSI-420 accounted for 10% of the total amount of erlotinib, more than double this ratio in the literature, indicating differences in the metabolism of erlotinib among the species.