An analytical method for irinotecan (CPT-11) and its metabolites using a high-performance liquid chromatography: parallel detection with fluorescence and mass spectrometry
An analytical method for irinotecan (CPT-11) and its metabolites using a high-performance liquid chromatography: parallel detection with fluorescence and mass spectrometry
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DOI：
10.1002/bmc.137
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发表时间：
2002-05-01
影响因子：
1.8
通讯作者：
Sawada, J
中科院分区：
文献类型：
--
作者：
Sai, K;Kaniwa, N;Sawada, J
伊立替康或7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin(CPT-11)是一种抗癌前药，用于治疗多种癌症。在这里，我们描述了CPT-11及其代谢物的分析方法的有效性，包括活性代谢物7-乙基-10-羟基喜树碱(SN-38)、其葡萄糖醛酸化形式SN-38G，以及几种细胞色素P450 3A介导的产物，如7-乙基-10-[4-N-(5-氨基戊酸)-1-哌啶基]羧氧基喜树碱(APC)，使用与平行荧光和质谱学检测系统连接的高效液相色谱。该方法的特点是：(1)用高氯酸/甲醇从生物材料中简单地提取分析物；(2)用荧光检测器(FLD)灵敏地定量主要代谢物(SN-38G、SN-38和APC)，其定量限分别为SN-38G和APC 2.5 ng/mL、CPT-11 5 ng/mL和SN-38 1 ng/mL；(3)用质量选择检测器(MSD)并行选择性监测包括次要代谢物在内的代谢物。预计联合给药的其他药物没有观察到干扰。通过鉴定人肝微粒体中产生的一种新的代谢物，证明了该方法的有效性。结果表明，FLD和MSD的结合能够对CPT-11及其代谢物进行高度选择性的分析，对于体内和体外的研究都是有用的。版权所有(C)2002 John Wiley Sons，Ltd.
Irinotecan or 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) is an anticancer pro-drug used in the treatment of many types of cancer. We describe here the validation of an analytical method for CPT-11 and its metabolites, including an active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38), its glucuronidated form, SN-38G, and several cytochrome P450 3A-mediated products such as 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC) using a high-performance liquid chromatography connected to parallel fluorescence and mass spectrometry detection systems. This method is characterized as follows: (1) simple extraction of the analytes from biomaterials with perchloric acid/methanol; (2) sensitive quantitation of major metabolites (SN-38G, SN-38 and APC) with a fluorescence detector (FLD), where the limits of quantitation by FLD were 2.5 ng/mL for SN-38G and APC, 5 ng/mL for CPT-11 and 1 ng/mL for SN-38, respectively; (3) parallel selective monitoring of the metabolites including minor metabolites with a mass selected detector (MSD). There was no observed interference by other drugs expected to be co-administered. This method showed its usefulness by identifying a novel metabolite produced in human hepatic microsomes. The results indicate that this combination of FLD and MSD enables a highly selective analysis of CPT-11 and its metabolites, and is useful for studies both in vivo and in vitro. Copyright (C) 2002 John Wiley Sons, Ltd.