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胶束电动毛细管色谱法揭示了脂质体阿霉素和游离阿霉素处理人白血病细胞后细胞内代谢的差异。

Micellar electrokinetic capillary chromatography reveals differences in intracellular metabolism between liposomal and free doxorubicin treatment of human leukemia cells.

作者信息

Eder Angela R, Arriaga Edgar A

机构信息

Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Dec 27;829(1-2):115-22. doi: 10.1016/j.jchromb.2005.09.038. Epub 2005 Oct 21.

Abstract

Doxil is a pegylated liposome formulation of the anthracycline doxorubicin. To better explain observed differences in the toxicity of Doxil and free doxorubicin in solution, the intracellular metabolism of the formulations after treatment in CCRF-CEM and CEM/C2 human leukemia cell lines was investigated. Using micellar electrokinetic capillary chromatography with laser-induced fluorescence detection, with a 63 zepto (10(-21)) mole doxorubicin limit of detection, five common metabolites and doxorubicin were detected upon treatment with both of these drug delivery systems. Two unique metabolites appeared with the Doxil and two unique metabolites appeared with the free doxorubicin delivery systems. For common metabolites, the relative amount of metabolite generated from Doxil was approximately 10 times higher than for free doxorubicin.

摘要

多柔比星脂质体(Doxil)是蒽环类药物多柔比星的聚乙二醇化脂质体制剂。为了更好地解释Doxil与溶液中游离多柔比星在毒性方面观察到的差异,研究了在CCRF - CEM和CEM/C2人白血病细胞系中处理后制剂的细胞内代谢情况。使用带有激光诱导荧光检测的胶束电动毛细管色谱法,多柔比星的检测限为63zepto(10⁻²¹)摩尔,在用这两种药物递送系统处理后检测到了五种常见代谢物和多柔比星。Doxil出现了两种独特的代谢物,游离多柔比星递送系统出现了另外两种独特的代谢物。对于常见代谢物,Doxil产生的代谢物相对量比游离多柔比星高约10倍。

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