title: Combination of micellar electrokinetic and high-performance liquid chromatographies to assess age-related changes in the in vitro metabolism of Fischer 344 rat liver.
abstract: 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.
authors: Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
authors: Yaohua
authors: Y
authors: Wang
authors: Joseph B
authors: JB
authors: Katzenmeyer
authors: Edgar A
authors: EA
authors: Arriaga
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D004317:Doxorubicin / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D008099:Liver / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000903:Antibiotics, Antineoplastic; D009249:NADP; D004317:Doxorubicin; D008274:Magnesium