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采用 HPLC-荧光法测定小鼠血浆和组织匀浆中伊立替康及其活性代谢物 SN-38 的生物分析方法。

Bioanalytical method for the simultaneous quantification of irinotecan and its active metabolite SN-38 in mouse plasma and tissue homogenates using HPLC-fluorescence.

机构信息

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; Division of Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jul 15;1149:122177. doi: 10.1016/j.jchromb.2020.122177. Epub 2020 May 19.

DOI:10.1016/j.jchromb.2020.122177
PMID:32464539
Abstract

A simple and rapid bioanalytical method was developed for the simultaneous quantification of irinotecan and SN-38 in mouse plasma and tissue homogenates using High-Performance Liquid Chromatography with Fluorescence detection (HPLC-FL). Camptothecin was used as internal standard and protein precipitation with acetonitrile-methanol (1:1, v/v) followed by acidification with 0.5 M hydrochloric acid was used for sample pre-treatment. The analytes and the internal standard were detected using an excitation and emission wavelength of 368 and 515 nm, respectively. The linearity, selectivity, accuracy and precision, carry-over, limit of detection and lower limit of quantification of the method are described. The method was linear from 7.5 to 1500 ng/mL for irinotecan and from 5 to 1000 ng/mL for SN-38. For all matrices, the accuracy bias and precision variation were within ±15% and ≤15%, respectively. This method was successfully applied to study the pharmacokinetics of irinotecan and SN-38 using in vivo mouse models.

摘要

建立了一种简单、快速的同时测定小鼠血浆和组织匀浆中伊立替康和 SN-38 的液质联用分析方法。采用高效液相色谱-荧光检测法(HPLC-FL),以喜树碱为内标,乙腈-甲醇(1:1,v/v)沉淀蛋白,并用 0.5 M 盐酸酸化进行样品预处理。用 368nm 和 515nm 的激发和发射波长分别检测分析物和内标。描述了该方法的线性、选择性、准确度和精密度、残留、检测限和定量下限。伊立替康在 7.5 至 1500ng/mL 范围内,SN-38 在 5 至 1000ng/mL 范围内呈线性。对于所有基质,准确度偏差和精密度变化均在±15%和≤15%范围内。该方法成功应用于体内小鼠模型研究伊立替康和 SN-38 的药代动力学。

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