Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
J Gerontol A Biol Sci Med Sci. 2011 Sep;66(9):935-43. doi: 10.1093/gerona/glr074. Epub 2011 Jul 11.
The metabolism of doxorubicin, a widely used anticancer drug, is different in young adult and old cancer patients. In this study, we demonstrate that micellar electrokinetic chromatography with laser-induced fluorescence detection is highly suited to monitor the metabolism of doxorubicin in subcellular fractions isolated from young adult (11 months, 100% survival rate) and old (26 months, ~25% survival rate) Fischer 344 rat livers. The relative amounts of doxorubicin metabolized in both mitochondria-enriched and postmitochondria fractions of young adult were larger than the respective fractions of old rat liver. 7-Deoxydoxorubicinolone and 7-deoxydoxorubicinone were identified using internal standard addition and structural elucidation by high-performance liquid chromatography with combined laser-induced fluorescence and mass spectrometry detection. Although high-performance liquid chromatography with combined laser-induced fluorescence and mass spectrometry detection is more useful in the identification of compounds, micellar electrokinetic chromatography with laser-induced fluorescence detection has low-sample requirements, simplified sample processing procedures, short analysis times and low limit of detection. Therefore, the combination of these two techniques provides a powerful approach to investigate metabolism of fluorescent drugs in aging studies.
多柔比星是一种广泛应用的抗癌药物，其在年轻成年和老年癌症患者中的代谢情况有所不同。在这项研究中，我们证明胶束电动色谱-激光诱导荧光检测非常适合监测从小鼠（11 个月，存活率 100%）和老年（26 个月，存活率约 25%）Fischer 344 大鼠肝脏分离的亚细胞部分中多柔比星的代谢情况。年轻成年大鼠的线粒体富集部分和线粒体后部分代谢的多柔比星的相对量大于老年大鼠的相应部分。通过内标添加和高效液相色谱-激光诱导荧光和质谱联用检测的结构阐明，鉴定了 7-脱氧柔红霉素酮和 7-脱氧柔红霉素酮。虽然高效液相色谱-激光诱导荧光和质谱联用检测在化合物鉴定方面更有用，但胶束电动色谱-激光诱导荧光检测具有样品需求低、样品处理程序简化、分析时间短和检测限低的特点。因此，这两种技术的结合为研究衰老过程中荧光药物的代谢提供了一种强有力的方法。
