Reliable determination of the main metabolites of 2-phenoxyethanol in human blood and urine using LC-MS/MS analysis.

2-Phenoxyethanol (PhE) is used as a broad-spectrum preservative in several consumer products like cosmetics and cleaning agents. To enable the analysis and assessment of human exposure to PhE, a fast and sensitive LC-MS/MS method for the quantification of two PhE metabolites, namely phenoxyacetic acid (PhAA) and 4-hydroxyphenoxyacetic acid (4-OH-PhAA) in human urine and blood was developed and validated. The method is based on liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). Sample preparation was different for both matrices: either a simple "dilute&shoot"-approach for urine samples or a liquid-liquid-extraction (LLE) for blood samples was used. The limit of quantification (LOQ) is 10 μg L-1 and 6 μg L-1 for PhAA and 20 μg L-1 and 10 μg L-1 for 4-OH-PhAA in urine and blood, respectively. The method was applied to urine samples of 153 persons without occupational exposure to PhE and to blood samples of 7 additional volunteers. In blood, PhAA was detected in 57% of all samples (range: <LOQ - 0.017 mg L-1), while 4-OH-PhAA was not detectable. In contrast to that, PhAA was found in 99% and 4-OH-PhAA in 95% of all urine samples. The median concentrations in urine were 0.99 mg L-1 (range: <LOQ - 53.83 mg L-1) for PhAA and 0.11 mg L-1 (<LOQ - 4.98 mg L-1) for 4-OH-PhAA, respectively. Analyses after acid hydrolysis showed that both urinary metabolites are excreted unconjugated.