Resolution of valproic acid from deuterated analogues and their quantitation in plasma using capillary gas chromatography.

Quantitation of valproic acid and a deuterated analogue in the same plasma sample by capillary gas chromatography without mass spectrometry was illustrated. Specificity was accomplished solely with a 60 m X 0.25 mm fused silica WCOT column coated with OV-351. A hexadeutero and two tetradeutero analogues of valproic acid had resolutions of at least 1.2 from valproic acid. Plasma samples were extracted with carbon tetrachloride following the addition of 2-ethylhexanoic acid as the internal standard. The method is sensitive to at least 0.5 microgram/ml and provides the capability of conducting absolute bioavailability and pulsed dosing studies with deuterated drug analogues without a mass spectrometer. The technique was applied to the analysis of plasma samples from dogs simultaneously administered valproic acid and a deuterated analogue.