Determination of plasma concentrations of epirubicin and its metabolites by high-performance liquid chromatography during a 96-h infusion in cancer chemotherapy.
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 beta-glucuronidase. The metabolites epirubicinol and 7-deoxydoxorubicinolone, but not 7-deoxydoxorubicinone, were also detected and measured.
Barker
I K
IK
Cancer Medicine Research Unit, Pharmaceutical Chemistry, School of Pharmacy, University of Bradford, UK.
Crawford
S M
SM
Fell
A F
AF
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000097:blood; D015251:Epirubicin / Q000008:administration & dosage* / Q000097:blood*; D006801:Humans; D007260:Infusion Pumps; D007700:Kinetics; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D009279:Naphthacenes / Q000097:blood; D012044:Regression Analysis; D015203:Reproducibility of Results
D000903:Antibiotics, Antineoplastic; D009279:Naphthacenes; C074869:7-deoxy-13-dihydroadriamycinone; C010012:adriamycin aglycone; D015251:Epirubicin; D004317:Doxorubicin