4,5-Dihydroxy-2-hexanone: A new metabolite of N-hexane and of 2,5-hexanedione in rat urine

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Abstract
Male Wistar rats were exposed to 2000 ppm n‐hexane or were treated with a single dose of 2,5‐hexanedione (200 mg kg−1). Analysis of the urine collected after both treatments revealed the formation of 4,5‐dihydroxy‐2‐hexanone via 5‐hydroxy‐2‐hexanone or 2,5‐hexanedione, respectively. Identification of this new n‐hexane metabolite included enzymatic hydrolysis of the excreted glucuronide, derivatization of the keto group with O‐methylhydroxyl‐amine, and subsequent GC–MS analysis. The chemical structure derived from the mass spectra obtained was confirmed by further analysis of the methoxime‐TMS derivatives and of deuterated 4,5‐dihydroxy‐2‐hexanone excreted after treating rats with 2,5‐[2H10]‐hexanedione. 4,5‐Dihydroxy‐2‐hexanone is proposed to be identical with a urinary constituent that is excreted by rats after n‐hexane exposure and is converted to 2,5‐dimethylfuran or 2,5‐hexanedione, respectively, depending on the conditions of urine treatment prior to GC‐MS analysis.