Observations on 6-MAM (6-Monoacetylmorphine) in Urine

Abstract

Heroin (diacetylmorphine) is made by acetylation of the 3 and 6 positions of the morphine molecule allowing it to rapidly cross the blood brain barrier. Once taken, it is rapidly de-acylated in two steps. First, the acetyl group from the 3 position is removed, forming 6-monoacetylmorphine (6-MAM). Second, the acetyl group on the 6 position is hydrolyzed, forming morphine. Although the major excreted products of heroin metabolism are morphine and morphine glucuronide, detection of heroin use is achieved by monitoring the presence of the intermediate metabolite 6-MAM in urine. The only source of this metabolite is heroin. The testing logic being that because of its short half-life there would only be minimal amounts of 6-MAM excreted. Workplace testing guidelines set the cut-off for 6-MAM at 10 ng/ml, implying that only 0.5% of the excreted morphine would be 6-MAM. Reviews of our urine samples positive for 6-MAM showed a significant number were above 1000 ng/mL. We attempted to determine the possible reason for the high 6-MAM urine concentrations.