A simple, rapid gas-liquid chromatographic procedure for the determination of valproic acid in serum.

A simple, rapid method for the gas-liquid chromatographic (GLC) determination of valproic acid in serum without prior derivatization on a Nukol wide-bore capillary column is presented. The method was determined to have a lower limit of detection (LOD) of 5 mg/L and a lower limit of quantitation (LOQ) of 10 mg/L; the method was linear up to 6000 mg/L. Within-run precision (expressed as percent coefficient of variation [CV]) for control specimens containing 60 mg/L and 120 mg/L was 4.3% CV (n = 10) and 3.0% CV (n = 10), respectively. The between-run precision of control sera analyzed over four week yielded 8% at 25 mg/L, 5% at 60 mg/L, and 3% at 120 mg/L. The absolute, uncorrected, analytical recoveries of valproic acid at 10, 32, and 120 mg/L were 97% (n = 5), 101% (n = 5), and 84% (n = 5), respectively. The absolute recovery of the internal standard was 97% (n = 9). Drugs commonly indicated for therapeutic monitoring and other serum constituents were found not to interfere with the procedure. The results of an intermethod comparison study of serum specimens analyzed by TDx immunoassay versus the presented GLC method demonstrated good correlation. At 95% confidence limits, no statistically significant differences were observed between results (p < 0.05). The method is particularly advantageous to toxicology laboratories because chromatography is performed on a polar GLC column that can be modified readily for the routine clinical analysis of other polar compounds such as ethylene glycol and other glycols.