METHANDROSTENOLONE METABOLISM IN HUMANS - POTENTIAL PROBLEMS ASSOCIATED WITH ISOLATION AND IDENTIFICATION OF METABOLITES

Methandrostenolone dose (amount and duration) and methods of isolation from urine can influence the identification and quantitation of methandrostenolone metabolites. Long-term use of methandrostenolone at high dosages led to the appearance of unmetabolized drug in the urine and contributed to the identification of a previously unreported metabolite, 3β,6§,17β-trihydroxy-17α-methyl-5§-1-androstene. Exposure of methandrostenolone in vitro to acid conditions induced a retropinacol rearrangement in the D-ring of the methandrostenolone molecule, causing the formation of 18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one in large amounts. The same acidic conditions led to the addition of a hydroxyl at the 6 position of the B-ring of either the retropinacol rearrangement products or native methandrostenolone resulting in the formation of 6β-hydroxy-18-nor-17, 17-dimethyl-1,4,13(14)-androstatrien-3-one,6α-hydroxy-18-nor-17,17-dimethyl-1,4,13(14)-androstatrien, 6β-17α-methyl-1,4-androstadien-3-one and 6α,17β-dihydroxy-17α-methyl-1,4-androstadien-3-one. Hydroxylation of native methandrostenolone at the 6 position also occurs endogenously. However, no evidence of an endogenous retropinacol rearrangement was found. Silylating agents alone can induce the formation of small amounts of 6β,17β-dihydroxy-17α-methyl-1,4-androstadien-3-one. Discrepancies between previously published reports on methandrostenolone metabolism in man are discussed and compared with an animal model. © 1990.