title: Distribution of free and conjugated morphine in body fluids and tissues in a fatal heroin overdose: is conjugated morphine stable in postmortem specimens?
abstract: The tissue distribution of free and conjugated morphine in a male individual who died after self-injection of heroin and methamphetamine was investigated, and the postmortem stability of morphine in the blood, liver and urine, and that of 6-monoacetylmorphine in the urine was determined. Confirmation and quantitation of morphine, 6-monoacetylmorphine and methamphetamine were performed by gas chromatography/mass spectrometry and gas chromatography, respectively. Blood levels of free and total morphine were very site-dependent with ranges of 462-1350 and 534-1570 ng/mL, respectively. Large amounts of total morphine, 5220, 4200, and 2270 ng/g, had accumulated in the stomach contents, liver, and lung, respectively. The concentration of free morphine in the cerebrospinal fluid was correlated very closely with that in the cerebrum. The proportion of free morphine in various fluids and tissues ranged from 23.0% to 98.8% of total morphine: less than 30% in the stomach contents and urine; 30-60% in the liver, cerebrospinal fluid, lung, and pericardial sac fluid; 61-90% in the spleen, right femoral muscle, myocardium, blood in the left and right ventricles of the heart, and right femoral vein blood; more than 91% in the right kidney and cerebrum. Detectable amounts of 6-monoacetylmorphine, 417 ng/mL and 78 ng/g, existed in the urine and stomach contents, respectively, indicating that this individual might have died within several hours after heroin injection. Methamphetamine concentrations in the blood were also site-dependent within the range 551-1730 ng/mL. In an in vitro experiment, free and conjugated morphine were stable in the blood and urine at 4, 18-22, and 37 degrees C for a 10-day study period. In the liver, however, conjugated morphine had been converted almost completely to free morphine at 18-22 and 37 degrees C by the end of the experiment, although it was stable at 4 degrees C. Urine 6-monoacetylmorphine, although degraded slightly at 37 degrees C, was stable at 4 and 18-22 degrees C during the experiment. Thus it appears that non-specific hydrolysis of conjugated morphine to free morphine would not occur in corpses at least for a few days after death. Femoral muscle may be a specimen of choice for roughly predicting the ratio of free to total morphine in blood even when blood specimens are not available, because the femoral muscle is relatively spared of both postmortem diffusion of drugs and bacterial invasion.
authors.affiliation: Department of Legal Medicine, Kochi Medical School, Japan.
authors.forename: F
authors.initials: F
authors.lastname: Moriya
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000328:Adult; D001826:Body Fluids / Q000737:chemistry*; D062787:Drug Overdose; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000737:chemistry; D009020:Morphine / Q000737:chemistry / Q000493:pharmacokinetics* / Q000506:poisoning*; D009022:Morphine Derivatives / Q000737:chemistry; D011180:Postmortem Changes; D014018:Tissue Distribution
chemical_list: D009022:Morphine Derivatives; D008694:Methamphetamine; D009020:Morphine; C026979:6-O-monoacetylmorphine