A micromethod for the on-column methylation of valproic acid by gas-liquid chromatography

We described a simple procedure for the flash heater methylation of valproic acid and cyclohexylacetic acid (internal standard) by gas-liquid chromatography (GLC). A small volume (100 microL) of sample is acidified with 10% perchloric acid and extracted into hexane. An aliquot is back extracted into 5% tetramethylammonium hydroxide (TMH). A 1 microL sample of the TMH layer is injected into the GLC equipped with flame ionization detector (FID) and a 6 ft x 2 mm i.d. - nickel column packed with 3% OV-17 on 80/100 mesh Supelcoport. The injector temperature is set at 350 degrees C to ensure methylation. Recoveries are greater than 95% of theoretical value. The linearity for calibration points between 15 and 180 microgram/mL is excellent (coefficient of correlation and determination greater than 0.9999). The procedure is rapid and sensitive and does not require a dedicated column in the gas chromatograph.