Browsing Theses and Dissertations School of Pharmacy by Author "Goldberger, Bruce A."
Measurement and interpretation of heroin, 6-acetylmorphine and morphine concentrations in biological tissues obtained from heroin users and heroin-related deathsGoldberger, Bruce A.; Caplan, Yale H. (1993)Understanding the role of heroin in heroin-related deaths was facilitated by the development of an assay for heroin and its metabolites in biological specimens. Recognizing heroin's susceptibility to rapid chemical and metabolic hydrolysis, procedures were developed for the efficient recovery of heroin, 6-acetylmorphine and morphine from tissues utilizing liquid-liquid and solid phase extraction. Aprotic solvents, mild elution solvents and an enzyme inhibitor were employed to ensure maximum analyte stability. Extracts were analyzed by gas chromatography/mass spectrometry. The assay was highly sensitive and specific for heroin and its metabolites. The limit of detection for each analyte was approximately 1 ng/mL. Specimens were collected and analyzed from twenty-one cases of death due to acute narcotic intoxication. The mode of death in these cases was categorized as rapid, delayed or undetermined. Compared to delayed deaths, rapid deaths were characterized by the following trends: higher mean concentrations of 6-acetylmorphine, free morphine and total morphine in blood; higher ratio of free to total morphine concentration in blood; lower mean concentrations of 6-acetylmorphine and morphine in urine; greater likelihood to detect 6-acetylmorphine in blood; and lesser likelihood to detect heroin in urine. In a detailed study of two heroin overdose cases, heroin was present only in urine specimens. Concentrations of 6-acetylmorphine in cerebrospinal fluid, spleen and brain were substantially higher than in blood, liver, lung and kidney. All specimens were positive for morphine. Hair analysis was used to corroborate prior heroin exposure. Hair specimens, collected from twenty heroin users and two heroin-related deaths, contained 6-acetylmorphine and morphine. Heroin was found in 7 of 20 heroin user specimens. Generally, the 6-acetylmorphine concentration in hair was higher than that of heroin or morphine. The identification of heroin and 6-acetylmorphine in biological tissues effectively established heroin use in cases of acute narcotic intoxication. These studies demonstrated that measurement of heroin and its metabolites provides useful information in the differential diagnosis of heroin-related deaths.