Simple method based on fluorescent detection for the determination of 4-hydroxycyclophosphamide in plasma.
Cyclophosphamide is a prodrug used both as a single drug and in combination chemotherapy. Cyclophosphamide is converted to its active metabolite (4-hydroxycyclophosphamide) by the cytochrome P450 enzymes. A liquid chromatography method including liquid-liquid extraction and protein precipitation in one step was developed to measure 4-hydroxycyclophosphamide in plasma. The 4-hydroxycyclophosphamide was stabilized and converted to a fluorescent dansylhydrazone derivative, which was chromatographed on a reverse-phase column and detected using a spectrofluorometric detector at excitation of 350 nm and emission of 550 nm. The limit of quantitation was 60 ng/mL and the between-day accuracy and precision were less than 9%. The method was applied to the analysis of plasma from patients who had received an intravenous infusion of 1 g/m(2) cyclophosphamide.
Griskevicius
Laimonas
L
Department of Medicine, Division of Hematology, Laboratory of Hematology, KFC Novum, Karolinska Institutet, Huddinge University Hospital, 141 86 Stockholm, Sweden.
Meurling
Lennart
L
Hassan
Moustapha
M
D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*; D016903:Drug Monitoring / Q000379:methods / Q000592:standards*; D005453:Fluorescence; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous; D015203:Reproducibility of Results
D007166:Immunosuppressive Agents; C012358:4-hydroxycyclophosphamide; D003520:Cyclophosphamide