High-performance liquid chromatographic method for the determination of AG-331, a novel anti-cancer agent, in human serum and urine using solid-phase extraction and photodiode-array detection

Mingxin Qian, Peter J. O'Dwyer, James M. Gallo

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

A reversed-phase isocratic high-performance liquid chromatographic method has been developed for the determination of AG-331, a novel thymidylate synthase inhibitor, in human serum and urine. The method involves a solid-phase extraction from C18 cartridges without addition of an internal standard. The methanol eluent is evaporated under nitrogen at 40°C, and reconstituted in mobile phase, acetonitrile-water (35:65, v/v) containing 25 mM ammonium phosphate. Separation of AG-331 was obtained on a C18 column at a flow-rate of 1 ml/min. Chromatographic signals were monitored by a photodiode-array detector at a primary wavelength of 457 nm with a bandwidth of 4.8 nm. Standard curves are linear in the range of 22-2175 ng/ml in plasma and 44-2175 ng/ml in urine, respectively. The extraction recovery ranged from 92.9-102.4%. Intra-day coefficient of variation was less than 9.5%, and inter-day coefficient of variation was less than 14.3% for an AG-331 concentration of 44 ng/ml. This method has been used to characterize the pharmacokinetics of AG-331 in cancer patients as part of ongoing Phase I trials.

Original languageEnglish
Pages (from-to)307-314
Number of pages8
JournalJournal of Chromatography B: Biomedical Sciences and Applications
Volume666
Issue number2
DOIs
StatePublished - 21 Apr 1995
Externally publishedYes

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