High-performance liquid chromatographic assay for the determination of the novel podophyllotoxin derivative dimethylaminoetoposide (NK611) in human plasma.
A simple, rapid and reproducible plasma assay for the determination of the novel epipodophyllotoxin derivative, dimethylaminoetoposide (NK611, I) and its N-demethyl metabolite (II) is reported. The method involves solid-phase extraction using an isolute C18 cartridge and HPLC separation on a reduced-activity C18 column (8 cm long) with a mobile phase of acetonitrile-water-0.1 M phosphoric acid (23:76:1, v/v/v); peaks are detected at 205 nm. The intra- and inter-day precision and accuracy are within 5 and 4% for I and II, respectively. The sensitivity is 20 ng/ml for both I and II. The assay is applicable to clinical pharmacokinetic studies. In one cancer patient who received both an oral and an intravenous dose of 10 mg of I the bioavailability was 82% and the clearance 20.8 ml/min.
Zucchetti
M
M
Mario Negri Institute for Pharmacological Research, Milano, Italy.
De Fusco
M
M
Sessa
C
C
Fröhlich
A
A
Reichert
S
S
D'Incalci
M
M
D000970:Antineoplastic Agents / Q000097:blood* / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D011786:Quality Control; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; C080080:NK 611; D011034:Podophyllotoxin