Determination of plasma concentrations of epirubicin and its metabolites by high-performance liquid chromatography during a 96-h infusion in cancer chemotherapy |
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Authors: | Ian K. Barker S. Michael Crawford Anthony F. Fell |
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Affiliation: | aCancer Medicine Research Unit, Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, Bradford BD7 1DP, UK;bPharmaceutical Analysis Research Unit, Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, Bradford BD7 1DP, UK |
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Abstract: | In order to determine epirubicin and its metabolites at low concentrations (<38 ng/ml) in small plasma samples, a fast reliable method based on a precipitation pre-treatment and sensitive reversed-phase isocratic HPLC has been developed and validated for epirubicin in the range 5–100 ng/ml. The R.S.D. was 5–9% over this concentration range. For human serum containing 25 ng/ml of epirubicin, the inter- and intra-day variation was <10%. Recoveries of the metabolites epirubicinol, 7-deoxydoxorubicinone and 7-deoxydoxorubicinolone at 20 ng/ml ranged from 94–104%. The assay has been used to study human plasma samples taken during a 96-h infusion of epirubicin in a patient with multiple myeloma. The combined levels of the unseparated metabolites, epirubicin glucuronide and epirubicinol glucuronide, were semiquantitatively determined after treatment with β-glucuronidase. The metabolites epirubicinol and 7-deoxydoxorubicinolone, but not 7-deoxydoxorubicinone, were also detected and measured. |
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Keywords: | Epirubicin Epirubicinol 7-Deoxydoxorubicinone 7-Deoxydoxorubicinolone 4′ -Epidoxorubicinone Doxorubicinone Doxorubicinolone |
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