Analysis of ethylene glycol ether metabolites in urine by extractive alkylation and electron-capture gas chromatography.

Alkoxyacetic acids are metabolically formed and excreted in urine after exposure to ethylene glycol monoalkyl ethers (alkoxyethanols) or their acetate esters. This paper presents a sensitive method based on extractive alkylation for determination of alkoxyacetic acids in urine. Alkoxyacetate ions were extracted from 200 microliters urine into methylene chloride, with tetrabutylammonium acting as counter ion, and derivatized with pentafluorobenzyl bromide in a single step. After separation of the methylene chloride phase, evaporation, and dissolution of the residues in hexane the esters were analyzed by fused silica capillary column gas chromatography and electron capture detection. The esters formed were stable for at least 2 weeks at room temperature. The limit of quantification was estimated to 2 microM (corresponding to an injected amount of 2 pg) for methoxyacetic (MAA) and ethoxyacetic acid (EAA) in urine. The corresponding values for butoxyacetic acid (BAA) were 4 microM and 5 pg, respectively. The detector response was linear up to 80 microM and the formation of derivative at least up to 1 mM. The method error may be reduced by using a second alkoxyacetic acid derivative, EAA, BAA or 2-pentoxyacetic acid (PAA), as an internal standard. The sensitivity, stability, reduced number of extractions, and small volumes of reagents and sample needed make the present method useful in biomonitoring of occupational exposure to ethylene glycol ethers.