Determination of pravastatin sodium and its major metabolites in human serum/plasma by capillary gas chromatography/negative ion chemical ionization mass spectrometry.

A capillary gas chromatography/negative ion chemical ionization mass spectrometry method has been developed to measure pravastatin sodium, an anti-hypercholesterolemic agent, and two of its major metabolites in human serum. Injected on a capillary column, derivatized pravastatin sodium and the two, metabolites were detected at levels of 0.5 pg microliters-1 injected with a signal-to-noise ratio of 3 to 1. The limit of detection was 0.3 ng ml-1 serum of each compound with 95% confidence using a weighted linear regression analysis. Prior to analysis, samples were purified on 200 mg C18 solid-phase extraction columns and derivatized with pentafluorobenzyl bromide and N,O-bis-(trimethylsilyl)-trifluoroacetamide. An excess of pentafluorobenzyl bromide was removed by reaction with propionic acid.