A major toxicological challenge is distinguishing whether morphine in urine, in the absence of 6‐monoacetylmorphine (6‐MAM), originates from ‘street’ heroin use or poppy seed ingestion. Manufacturing byproducts from the synthesis of illicit heroin include those that originate from the reaction of acetic anhydride with the alkaloid impurity, thebaine, which undergoes skeletal rearrangement, resulting in compounds with a 2‐(N‐methylacetamido)ethyl side‐chain. The hypothesis that the tertiary amide in this side‐chain is resistant to endogenous hydrolysis was supported from in‐vitro experiments; a glucuronide metabolite (designated ‘ATM4G’) was identified that may be used as a marker of ‘street’ heroin administration. Liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) analysis for this metabolite was then performed on selected urine specimens from 22 known heroin users, these being negative on routine testing for 6‐MAM by gas chromatography‐mass spectrometry (GC‐MS), using the generally applied reporting threshold of 10 ng/mL, but positive for the presence of morphine. Peaks corresponding to the retention time for the metabolite marker were clearly observed for 16 of the 22 samples, with variations of the ratios of its three dependent ions being within ± 30% of that produced in vitro. Conversely, 6‐MAM was detected in only 3 samples, but at concentrations <1 ng/mL. Such a high frequency for the presence of the metabolite marker in urine, in the absence of 6‐MAM, is noteworthy and suggests that detection of this metabolite may offer an important advance in forensic toxicology, allowing the development of a new and more definitive test for heroin abuse and thus a potential solution to the so‐called ‘poppy seed defense’. Copyright © 2013 John Wiley & Sons, Ltd.