Water-promoted formation of phenylboronates of 1,3-diols during gas-liquid chromatographic analysis: application to the assay of meprobamate

Abstract

A simple method for the assay of the hypnotic drug meprobamate (2-methyl-2-propylpropane-1,3-diol dicarbamate) in plasma has been developed. Hydrolysis to the 1,3-diol was followed by extraction into an organic solvent and, after mixing with phenylboronic acid in methanol-water (2 + 1), a portion (1–2 µl) of the extract was analysed directly by gas-liquid chromatography with flame ionisation detection using a column packed with 3%m/m OV-101 at 160 °C. Mebutamate (2-methyl-2-sec-butylpropane-1,3-diol dicarbamate) was used as a reactive internal standard. The limit of accurate measurement was 5 mg l^–1[intra-assay coefficient of variation 5.2%(n= 10)] and the assay calibration was linear up to 200 mg l^–1. The inter-assay coefficient of variation was 3.7% at 60 mg l^–1(n= 10). The finding that water acts to promote phenylboronate formation under the conditions described may prove useful when analysing other 1,2- and 1,3-diols and, possibly, other polar bifunctional compounds by gas-liquid chromatography.