Methandrostenolone metabolism in humans: Potential problems associated with isolation and identification of metabolites

Abstract

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.