Sensitive method for the determination of daunorubicin and all its known metabolites in plasma and heart by high-performance liquid chromatography with fluorescence detection

J. De Jong, P. A. Maessen, A. Akkerdaas, S. F. Cheung, H. M. Pinedo, W. J F Van Der Vijgh

Research output: Contribution to journalArticle

Abstract

The cytostatic agent daunorubicin is effective against leukaemia. An important side-effect is cardiomyopathy, common to all anthracyclines. Since anthracycline metabolites are thought to contribute to the observed cardiotoxicity, a method for the quantitative determination of all metabolites in plasma as well as in tissues is needed as a basis for the further investigation of the correlation between toxicity and the amount of each metabolite formed. Using Sep-Pak C18 cartridges we were able to extract daunorubicin and its five metabolites, including the aglycones, with recoveries in the range 50-90%. Depending on the chemical properties of each metabolite, fluorescence detection following high-performance liquid chromatographic separation permitted detection limits as low as 0.2-0.9 nM in plasma and 0.8-3·10-11 mol/g in tissue, at a signal-to-noise ratio of 2, which compare favourably with literature data. The method showed linearity in the ranges 1-250 nM in plasma and 0.04-4.0 nmol/g in tissue (r ≥ 0.998). The accuracy, determined at 10 and 100 nM for plasma and at 0.1 and 1.0 nmol/g for tissue, was in the range 86-103 and 85-110% for plasma and tissue, respectively. The within-day and between-day repeatability values were acceptable (between 2 and 12%). Because of large inter-compound differences, separate calibration curves were used for each anthracycline. Application of the assay to the analysis of plasma and tissue samples of mice after intravenous injection of daunorubicin proved successful.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume529
Issue numberC
DOIs
StatePublished - 1990
Externally publishedYes

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Daunorubicin
High performance liquid chromatography
Metabolites
Fluorescence
High Pressure Liquid Chromatography
Tissue
Plasmas
Anthracyclines
Cytostatic Agents
Signal-To-Noise Ratio
Cardiomyopathies
Intravenous Injections
Chemical properties
Calibration
Toxicity
Limit of Detection
Assays
Signal to noise ratio
Leukemia
Recovery

ASJC Scopus subject areas

  • Chemistry(all)
  • Clinical Biochemistry
  • Molecular Medicine

Cite this

Sensitive method for the determination of daunorubicin and all its known metabolites in plasma and heart by high-performance liquid chromatography with fluorescence detection. / De Jong, J.; Maessen, P. A.; Akkerdaas, A.; Cheung, S. F.; Pinedo, H. M.; Van Der Vijgh, W. J F.

In: Journal of Chromatography B: Biomedical Sciences and Applications, Vol. 529, No. C, 1990, p. 359-368.

Research output: Contribution to journalArticle

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abstract = "The cytostatic agent daunorubicin is effective against leukaemia. An important side-effect is cardiomyopathy, common to all anthracyclines. Since anthracycline metabolites are thought to contribute to the observed cardiotoxicity, a method for the quantitative determination of all metabolites in plasma as well as in tissues is needed as a basis for the further investigation of the correlation between toxicity and the amount of each metabolite formed. Using Sep-Pak C18 cartridges we were able to extract daunorubicin and its five metabolites, including the aglycones, with recoveries in the range 50-90{\%}. Depending on the chemical properties of each metabolite, fluorescence detection following high-performance liquid chromatographic separation permitted detection limits as low as 0.2-0.9 nM in plasma and 0.8-3·10-11 mol/g in tissue, at a signal-to-noise ratio of 2, which compare favourably with literature data. The method showed linearity in the ranges 1-250 nM in plasma and 0.04-4.0 nmol/g in tissue (r ≥ 0.998). The accuracy, determined at 10 and 100 nM for plasma and at 0.1 and 1.0 nmol/g for tissue, was in the range 86-103 and 85-110{\%} for plasma and tissue, respectively. The within-day and between-day repeatability values were acceptable (between 2 and 12{\%}). Because of large inter-compound differences, separate calibration curves were used for each anthracycline. Application of the assay to the analysis of plasma and tissue samples of mice after intravenous injection of daunorubicin proved successful.",
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