Gas chromatography analysis of urinary alkoxyacetic acids as biomarkers of exposure to aliphatic alkyl ethers

Analysis of alkoxyacetic acids has received considerable research interest in toxicology because these compounds have been reported as metabolites and biomarkers of exposure to widely used industrial chemicals such as alkyl-substituted ethylene glycols and other aliphatic ethers. This paper describes an improved method for the determination of methoxyacetic acid (MAA), ethoxyacetic acid (EAA), and butoxyacetic acid (BAA) in rat urine. Solid-phase extraction with Bakerbond(T) C18 bonded silica cartridges was successfully employed to isolate the acids from rat urine. The acids were then converted to methyl esters with diazomethane derivatization and analyzed using a gas chromatograph (GC) equipped with a mass spectrometry (MS) and a GC with flame ionization detector (FID). Employing GC-MS under selected ion monitoring detection, the lowest detection concentrations for MAA, EAA, and BAA were determined to be from 2 to 4 ng/mL urine in 1 mL of sample size. This method is 5 to 10 times more sensitive than that using GC-FID. The method described here is superior to the existing ones reported in the literature in that it employs an easy sample treatment procedure and gives much higher recoveries, making it suitable for routine assays. The utility of this new method was demonstrated in a toxicology study of aliphatic alkyl ethers.