Method for the simultaneous quantification of n-hexane metabolites: application to n-hexane metabolism determination

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Abstract
1 The described analytical procedure permits the simultaneous determination of the main n-hexane meta bolites in urine. 2-Hexanone, 2-hexanol, 2, 5-hexanediol and 2, 5-hexanedione, were chosen to dose the rats used in this study. All urine samples were collected and analysed on a daily basis, before and after acidic hydrolysis (pH 0.1) by GC/MS. 2-Hexanone, 2, 5-dimethylfurane, γ-valerolac tone and 2, 5-hexanedione were determined before hydro lysis ; 2-hexanol and 2, 5-hexanediol, after hydrolysis; and 5-hydroxy-2-hexanone and 4, 5-dihydroxy-2-hexanone were calculated by the difference between γ-valerolactone and 2, 5-hexanedione with and without hydrolysis, respectively. 2 A metabolic scheme was proposed reflecting the biotransformations undergone by the four compounds assayed. We consider 2, 5-dimethylfurane as a 'true metabolite' because the quantities detected were always greater before hydrolysis. 3 It has been reported that human and rat n-hexane metabolism follow a similar pattern. Therefore, as a practical application and without increasing either sample or time requirements, the simultaneous quantifi cation of the different metabolites and their excretion profile could provide better information about the metabolic situation of exposed workers than the determi nation of 2, 5-hexanedione alone. According to our experimental results, 4, 5-dihydroxy-2-hexanone itself would be a good toxicity indicator.