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Development of a bioanalytical liquid chromatography method for quantitation of 9-nitrocamptothecin in human plasma
Murugesan K Gounder1, Show-Li Sun, Howard Sands
1Department 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
Abstract:
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.
