In Vitro Formation of Acetylmorphine from Morphine and Aspirin in Postmortem Gastric Contents and Deionized Water

Forensic toxicologists consider detection of 6-acetylmorphine (6-AM) definitive evidence of heroin abuse. This study investigated the possibility that aspirin, when in solution with morphine, may acetylate morphine to produce acetylmorphine (AM). Morphine sulfate-extended release tablets (15 mg) and aspirin (325 mg) tablets were incubated in 50 mL postmortem gastric contents or deionized water at 37°C. One-milliliter aliquots were taken at timed intervals, extracted by solid-phase extraction, derivatized and analyzed by the gas chromatograph with a mass selective detector. Both 3- and 6-AM were detected in samples containing morphine and aspirin in combination; no heroin was detected. Production of AM was pH dependent with optimal formation at pH ≥4. In gastric contents, concentrations of 3-AM exceeded that of 6-AM by ∼10-fold. Production of 3-AM in gastric contents was approximately twice as high as it was in water, while matrix did not appear to affect 6-AM production. Urine specimens (10,602) assayed at a pain management laboratory and postmortem cases (>6,000) were investigated for in vivo formation of AM. Three cases exhibited unexplained 6-AM results. These data indicate that in vivo formation of 6-AM from the co-administration of aspirin and morphine, if it happens, is quite rare. In instances where this is suspected, 3-AM should be monitored.