Determination of clovoxamine concentration in human plasma by electron capture gas chromatography

The antidepressant drug clovoxamine can be specifically and sensitively quantitated in human plasma by electron capture gas chromatography. Clovoxamine and the internal standard fluvoxamine are extracted into ethyl acetate from plasma at pH 12, back-extracted into phosphoric acid, and hydrolyzed at 90 degrees C to form ketone derivatives, which are then re-extracted into hexane for injection into the chromatograph. As little as 1 microgram of clovoxamine per liter of plasma can be measured. The coefficients of variation (CV) for th analysis at concentrations of 10 and 100 micrograms/L are respectively: within-run, 5.4% and 2.7%; between-run, 17.5% and 7.0%. When this assay was applied to plasma from individuals involved in an early clinical trial of clovoxamine, steady-state plasma concentrations ranged from 50 to 77 micrograms/L 3 h after a 50-mg oral dose of clovoxamine fumarate.