Further studies of metyrapone effects upon anilide hydroxylation

The enhancing effect of metyrapone upon the p-hydroxylation of acetanilide has been confirmed with the use of a new gas-chromatographic method for the determination of acetaminophen. This effect has been shown not to be due to inhibition of hydrolysis of acetaminophen or interference with its determination, or to preferential formation of other phenolic metabolites. This effect of metyrapone is remarkably substrate-specific: phenol formation from the homologues of acetanilide, formanilide and propionanilide, and that from the sulfonamide analog of acetanilide, methanesulfonanilide, is inhibited by metyrapone over the concentration range in which acetanilide hydroxylation is enhanced. The same substrate specificity was observed when the modifier was acetophenone. alpha,alpha'-Dipyridyl, however, enhances phenol formation from all three carbonacylanilides, but does not affect that from methanesulfonanilide.