Analysis of intracellular doxorubicin and its metabolites by ultra-high-performance liquid chromatography

Doxorubicin, a highly effective anticancer drug, produces severe side effect such as cardiotoxicity, which is mainly caused by its metabolite, doxorubicinol. While in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2010-06, Vol.878 (19), p.1466-1470
Main Authors: Sakai-Kato, Kumiko, Saito, Eiko, Ishikura, Keiko, Kawanishi, Toru
Format: Article
Language:English
Subjects:
Analysis
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Doxorubicin
Doxorubicin - analogs & derivatives
Doxorubicin - analysis
Doxorubicin - chemistry
Doxorubicinol
Fundamental and applied biological sciences. Psychology
General pharmacology
HeLa Cells
HT29 Cells
Humans
Intracellular Space
Linear Models
Medical sciences
Pharmacology. Drug treatments
Sensitivity and Specificity
Ultra-high-performance liquid chromatography
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Summary:Doxorubicin, a highly effective anticancer drug, produces severe side effect such as cardiotoxicity, which is mainly caused by its metabolite, doxorubicinol. While in vitro studies by measuring cellular concentration of doxorubicin have been reported, there have been no reports on measuring cellular concentration of the metabolites. In this report, we developed a sensitive and high-throughput method for measuring cellular concentrations of doxorubicin and its metabolites by ultra-high-performance liquid chromatography. The method achieved more than 96% recovery of doxorubicin and its metabolites from cell homogenates. Using simple separation conditions, doxorubicin and its three main metabolites, and the internal standard, were separated within 3 min. The method has a limit of quantification of 17.4 pg (32.0 fmol) injected doxorubicin. This high sensitivity enables the detection and intracellular quantification of doxorubicin and its metabolite, doxorubicinol, in cell homogenates, and its use will facilitate studies of the relationship between doxorubicin pharmacokinetics and therapeutic outcome.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2010.03.040