High-performance liquid chromatographic assay for the determination of the novel etoposide derivative dimethylaminoetoposide (NK611) and its metabolites in urine of cancer patients.
A simple, reproducible and specific urine assay for the novel epipodophyllotoxin derivative dimethylaminoetoposide (NK611, I) its picro form (III), the N-demethyl metabolite (II) and its picro form (IV) is reported. The method involves the addition of Pr-NK611 as internal standard, chloroform extraction and HPLC separation on a Nova-Pak C18 column with a mobile phase of acetonitrile-0.05 M KH2PO4 (pH 6.4) (23:77, v/v). UV detection was used with absorbance monitored at 205 nm and the limit of quantification was 100 ng/ml. The intra- and inter-day precisions were within the ranges 1.1-3.4% and 1.9-2.4% for all analytes and the accuracy was 101-107%. The extraction recovery was more than 88% for I, II and IV and more than 83% for III. The assay is applicable to the urinary monitoring of I-IV in clinical pharmacokinetic investigations.
De Fusco
M
M
Laboratory of Cancer Chemotherapy, Mario Negri Institute for Pharmacological Research, Milan, Italy.
D'Incalci
M
M
Gentili
D
D
Reichert
S
S
Zucchetti
M
M
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007275:Injections, Intravenous; D009369:Neoplasms / Q000188:drug therapy / Q000652:urine*; D011034:Podophyllotoxin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000652:urine; D011786:Quality Control; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; C080080:NK 611; D011034:Podophyllotoxin