Abstract
A method has been developed for the determination of 2-t-butyl-4-methoxyphenol (BHA) and its metabolite di-BHA in rat plasma and tissues using gas chromatography-mass spectrometry with selected ion detection. Deuterium labeled BHA-d3 and di-BHA-d6 were synthesized and added to the tissue specimens as internal standards before methylene chloride extraction. The extracted compounds were derivatized with trifluoroacetic anhydride and analyzed by selected ion monitoring. Rat plasma and intestine concentrations of BHA and di-BHA at different times (0.15-24 hr) following the oral administration of a single dose of BHA (2 g X kg-1 body weight) were determined. Both BHA and di-BHA were present in all the analyzed samples, their concentration peaking within 1 hr after treatment. While in the intestine BHA levels were about 10 times higher than those of di-BHA, in the plasma they were between 100 and 15 times higher. These findings indicate that rat intestine is capable of transforming in vivo BHA into di-BHA and suggest that this organ is the major site where this transformation occurs.
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2,2'-dihydroxy-3,3'-di-t-butyl-5,5'-dimethoxydiphenyl, a new metabolite of 2-t-butyl-4-methoxyphenol in the rat.
