Metabolic kinetics of tert-butylhydroquinone and its metabolites in rat serum after oral administration by LC/ITMS.

Liquid chromatography-ion trap mass spectrometry (LC/ITMS) was employed for a metabolic kinetics study of tert-butylhydroquinone (TBHQ) and its metabolites in rat serum after oral administration. The mean serum concentration-time data of TBHQ and its four metabolites (M1-M4) in both male and female rats after oral administration of TBHQ at dosages of 7, 350 and 700 mg/kg were all best-fitted by a two-compartment model with first-order absorption. TBHQ was rapidly absorbed, distributed and metabolized. The metabolites were also distributed rapidly except M2, but eliminated more slowly than TBHQ. At the doses of 350 and 700 mg/kg, the total concentrations of TBHQ and its metabolites in serum were much higher for male than female rats during the metabolic process (P < 0.01). In addition, the serum concentrations of M1, M3 and M4 were all much higher for males than for females (P < 0.01) during the metabolic process, while no significant differences between male and female rats were found (P > 0.05) for TBHQ and M2, at the doses of 350 and 700 mg/kg. The exploratory assessment of dose proportionality for TBHQ and its metabolites by the power model indicated that the TBHQ exposure increased in a more-than-dose-proportional manner, but the exposures of the metabolites M1-M4 increased in a less-than-dose-proportional manner, across the dose of 7-700 mg/kg.