Development of a bioanalytical liquid chromatography method for quantitation of 9-nitrocamptothecin in human plasma.
9-Nitrocamptothecin (9-NC) is an orally administered camptothecin (CPT) that is under evaluation in clinical trials. This compound is not fluorescent, which has hampered development of a sensitive high-performance liquid chromatographic (LC) assay for measurement of drug concentrations in clinical trials. We now report development of an assay that involves reduction of 9-NC to the fluorescent compound 9-aminocamptothecin (9-AC). The method is based on enzymatic reduction of 9-NC using bovine liver S-9 fraction. This method is validated to quantitate 9-NC and 9-AC in patient samples, and yields results comparable to those obtained with an LC/MS method.
Gounder
Murugesan K
MK
Department of Pharmacology, Robert Wood Johnson School of Medicine, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA. goudemk@umdnj.edu
Sun
Show-Li
SL
Sands
Howard
H
Lin
Yong
Y
Shih
Weichung J
WJ
Gu
Zheming
Z
Charles-Williams
Samantha
S
Roychowdhury
Moulakshi
M
Rajendra
Rajeev
R
Rubin
Eric H
EH
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D001711:Biotransformation; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood*; D002417:Cattle; D006801:Humans; D008099:Liver / Q000378:metabolism; D012015:Reference Standards; D015203:Reproducibility of Results
D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin