Metabolism of minocycline in humans.

Metabolites of tetracycline antibiotics have not previously been isolated from human excreta. It is now demonstrated that minocycline is the first tetracycline to be metabolized in man. A two-step liquid chromatographic procedure was used to isolate three metabolites from human urine. The principal metabolite was tentatively identified as 9-hydroxyminocycline by mass spectral and spectrophotometric analysis and comparison with a synthetic compound. The latter was prepared by incubation of minocycline in a modified Udenfriend system, simulating an enzymatic oxygenase. Two other major metabolites are probably mono-N-demethylated derivatives. Substantial amounts of 4-epiminocycline, which probably resulted from minocycline epimerization rather than biotransformation, were also present.