HPLC-accelerator MS measurement of atrazine metabolites in human urine after dermal exposure

Metabolites of atrazine were measured in human urine after dermal exposure using HPLC to separate and identify metabolites and accelerator mass spectr ometry (AMS) to quantify them, Ring-labeled [C-14]atrazine was applied for 24 h with a dermal patch to human volunteers at low (0.167 mg, 6.45 mu Ci) and high (1.98 mg, 24.7 mu Ci) doses. Urine was collected for 7 days. The m ine was centrifuged to remove solids, and the supernatant was measured by l iquid scintillation counting prior to injection on the HPLC to ensure that <0.17 Po (4.5 pCi) was injected on the column. A reversed-phase gradient of 0.1% acetic acid in water and 0.1% acetic acid in acetonitrile became less polar with increasing time and separated the parent compound and major atr azine metabolites over 31 min on an octadecylsilane column. Peaks were iden tified by coelution with known standards. Elution fractions were collected in 1-min increments; half of each fraction was analyzed by AMS to obtain li mits of quantitation of 14 amol. Mercapturate metabolites of atrazine and d ealkylated atrazine dominated the early metabolic time points, accounting f or similar to 90% of the 14C in the urine. No parent compound was detected. The excreted atrazine metabolites became:more polar with increasing time, and an unidentified polar metabolite that was present in all samples became as prevalent as any of the known ring metabolites several days after the d ose was delivered. Knowledge of metabolite dynamics is crucial to developin g useful assays for monitoring atrazine exposure in agricultural workers.