Determination of SQ 33,600, a phosphinic acid containing HMG CoA reductase inhibitor, in human serum by high-performance liquid chromatography combined with ionspray mass spectrometry

Abstract

A method for the determination of SQ 33,600 in human serum is presented. This compound, which contains both carboxylic and phosphinic acid functional groups, is an HMG CoA reductase inhibitor currently under clinical investigation at the Bristol-Myers Squibb Pharmaceutical Research Institute. Human serum extracts prepared using solid-phase techniques were analyzed by combining high-performance liquid chromatography and atmospheric pressure ionization mass spectrometry. Under the conditions of the analysis, SQ 33,600 and its fluorinated analog, SQ 33,547, used as the internal standard, existed as anions in solution and could be sampled directly using the ionspray technique. The method utilized a simple isocratic mobile-phase system. No sample derivatization was required for these polar molecules. The retention time of the analytes was 3.5 min with a total analysis time of 5 min. The limit of detection was 0.5 ng ml⁻¹ serum with a minimum quantifiable limit of 2.0 ng ml⁻¹. The method was linear to at least 400 ng ml⁻¹.