Reliable quantitation of β-hydroxyethoxyacetic acid in human urine by an isotope-dilution GC-MS procedure

An analytical method for the determination of β-hydroxyethoxyacetic acid (HEAA), the main urinary metabolite of 1,4-dioxane was developed and validated. The presented method involves liquid-liquid extraction of HEAA from the urine samples, followed by silylation and subsequent analytical separation and detection using GC-MS. The method is characterized by its simple and fast sample preparation in combination with a robust chromatography. The use of isotope dilution analysis enables an efficient compensation of matrix related effects and analyte losses due to sample workup. The excellent reliability and reproducibility of the method is demonstrated by the good accuracy and precision data. Within-day precision and day-to-day precision ranged from 0.6 to 1.2% and 1.5 to 2.6%, respectively. The mean relative recovery of the method was found to be 98-101%. The LOD and LOQ of HEAA were determined to be 0.2 mg/L and 0.6 mg/L, respectively. In summary, the presented analytical method is well suited to be used for routine biomonitoring of occupational exposure to 1,4-dioxane.