Sensitive liquid chromatographic assay for the basic DNA intercalator (N,N-dimethylaminoethyl)-9-amino-5-methylacridine-4-carboxamide and its nitroarylmethyl quaternary prodrugs in biological samples.

TitleSensitive liquid chromatographic assay for the basic DNA intercalator (N,N-dimethylaminoethyl)-9-amino-5-methylacridine-4-carboxamide and its nitroarylmethyl quaternary prodrugs in biological samples.
Publication TypeJournal Article
Year of Publication2001
AuthorsFerry DM, van Zijl PL, Wilson WR
JournalJournal of chromatography. B, Biomedical sciences and applications
Volume763
Issue1-2
Pagination149-56
Date Published2001 Nov 5
Abstract

Nitroarylmethyl quaternary (NMQ) ammonium salts of the basic DNA intercalator AMAC (N,N-dimethylaminoethyl-9-amino-5-methylacridine-4-carboxamide) are of interest as anticancer prodrugs. A sensitive HPLC assay has been developed for quantitation of AMAC and its NMQ prodrugs in cultured cells, plasma and tissue. Recovery of the prodrugs, without conversion to AMAC, was achieved using extraction in alkaline acetonitrile followed by immediate reneutralisation. Reversed-phase HPLC with fluorescence detection gave a detection limit of 3 fmol for AMAC, with linearity to 20 nmol (using diode array absorbance at high concentrations). This assay was used to measure cellular uptake, and hypoxic metabolism to AMAC, of three NMQ-AMAC prodrugs.

Alternate JournalJ. Chromatogr. B Biomed. Sci. Appl.