Practical approach for high-performance liquid chromatographic method development: assaying synthetic intermediates of a leukotriene inhibitor

Abstract

High-performance liquid chromatographic (HPLC) methods for analyzing new drugs and their synthetic intermediates are needed as the synthesis is optimized and scaled up from making milligram amounts for initial evaluation of biological activity to producing kilogram amounts of the drug for thorough testing purposes. The most efficient solution is a single HPLC method that can be used for each step of the synthesis. A practical approach for the development of a single HPLC method is the use of computer-assisted method development to maximize the resolution within a reasonable analysis time. The computer program DryLab I was used in the development of an HPLC assay for the synthetic intermediates of a leukotriene inhibitor. The use of DryLab I with binary mixtures of organic solvents in the organic portion of reversed-phase HPLC systems is reported. With the retention data from two initial analyses, resolution can be optimized as a function of solvent strength.