Simultaneous determination of the lactone and carboxylate forms of the camptothecin derivative CPT-11 and its metabolite SN-38 in plasma by high-performance liquid chromatography
Simultaneous determination of the lactone and carboxylate forms of the camptothecin derivative CPT-11 and its metabolite SN-38 in plasma by high-performance liquid chromatography
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DOI：
10.1016/s0378-4347(98)00270-9
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发表时间：
1998-10-23
期刊：
影响因子：
--
通讯作者：
Mazzo, DJ
中科院分区：
文献类型：
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作者：
Chollet, DF;Goumaz, L;Mazzo, DJ
CPT-11(伊立替康)及其主要代谢产物SN-38是喜树碱的有效抗肿瘤衍生物。由于CPT-11和SN-38的活性内酯形式与各自效力较低的开环羟基酸物种存在PS依赖的平衡，因此同时监测这两种形式的两种化合物是相关的。CPT-11和SN-38衍生物具有完全不同的荧光响应。为了避免在波长设置上的任何妥协，我们开发了允许简单的自动波长设置更改的色谱条件，这是使用传统C-18柱的现有方法所阻止的。这是通过SymmetryC-18柱和梯度洗脱程序相结合的方式实现的，使用乙腈和75 mM醋酸铵+7.5 mM四丁基溴化铵在pH 6.4下进行洗脱。所开发的条件允许适合于关于可靠的峰积分的简单的自动波长改变的洗脱顺序。分别在波长ex=362 nm/lambda(Em)=425 nm和lambda(Ex)=375 nm/lambda(Em)=560 nn处检测到CPT-11和SN-38衍生物。所建立的方法可以检测柱上进样的每一种衍生物的量小于3pg。该方法已成功应用于大鼠和犬体内的药代动力学和毒代动力学研究。(C)1998年爱思唯尔科学公司。版权所有。
CPT-11 (irinotecan) and mainly its metabolite SN-38 are potent antitumor derivatives of camptothecin. As the active lactone forms of both CPT-11 and SN-38 exist in ps-dependent equilibrium with their respective less potent open-ring hydroxy acid species, the simultaneous monitoring of both forms of both compounds is relevant. CPT-11 and SN-38 derivatives have quite different fluorescence responses. In order to avoid any compromise on the wavelength setting, we developed chromatographic conditions allowing simple automated wavelength setting changes which have been prevented using existing methods involving conventional C-18 columns. This was achieved by means of a Symmetry C-18 column combined to a gradient elution program using acetonitrile and 75 mM ammonium acetate plus 7.5 mM tetrabutylammonium bromide at pH 6.4. The developed conditions allowed an elution order suitable for a simple automated wavelength change in respect to reliable peak integration. CPT-11 and SN-38 derivatives were detected at lambda(ex) = 362 nm/lambda(em) = 425 nm and lambda(ex) = 375 nm/lambda(em) = 560 nn, respectively. The developed method allowed the detection of amounts less than 3 pg of each derivative injected on column. The method was successfully applied to pharmacokinetic and toxicokinetic studies in rat and dog. (C) 1998 Elsevier Science BN. All rights reserved.