Journal Article

Urinary Excretion Profiles for Total Morphine, Free Morphine, and 6-Acetylmorphine Following Smoked and Intravenous Heroin*

Michael L. Smith, Eric T. Shimomura, Jacquelyn Summers, Buddha D. Paul, Amanda J. Jenkins, W. David Darwin and Edward J. Cone

in Journal of Analytical Toxicology

Volume 25, issue 7, pages 504-514
Published in print October 2001 | ISSN: 0146-4760
Published online October 2001 | e-ISSN: 1945-2403 | DOI: http://dx.doi.org/10.1093/jat/25.7.504
Urinary Excretion Profiles for Total Morphine, Free Morphine, and 6-Acetylmorphine Following Smoked and Intravenous Heroin*

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Heroin is one of the major target drugs in workplace drug-testing programs because of its history of abuse, liability, and continued negative social impact. This study was a comprehensive examination of pharmacokinetics, pharmacodynamics, detection times, opiate immunoassay performance, and urine excretion profiles following single doses of heroin administered to human subjects via smoking and intravenous routes. Studies of the first four components of this investigation were previously published. This article describes the urine excretion profiles. Total morphine (Tmor), free morphine (Fmor), and 6-acetylmorphine (6-AM) were measured by gas chromatography-mass spectrometry (GC-MS) in 920 urine samples collected from 11 male human subjects following single doses of heroin. Eight received intravenous doses of 3, 6, and 12 mg heroin HCl and four smoked 3.5-, 5.2-, 7-, 10.5-, or 13.9-mg doses of heroin (base). In addition, 183 urine-based blind quality-control samples were added to the study set to assess assay performance. Creatinine was also measured in each sample by a colorimetric technique. The parameters studied were not significantly dependent on route of administration. Excretion half-life mean ± SD for Tmor was 3.11 ± 0.30 h. Range (median) of peak urine concentrations, time to peak, time to last positive sample for low cutoff (300 ng/mL) and high cutoff (2000 ng/mL) for Tmor following lower doses (≤ 7 mg) were, respectively, 1392–9250 (3620) ng/mL, 1.2–6.2 (2.3) h, 7.4–31.9 (7.4) h, and 0–10.1 (4.3) h. Following higher doses (> 10 mg) they were 2065–29,030 (16,470) ng/mL, 2.3–9.3 (4.5) h, 10.7–53.5 (34.4) h, 2.3–22.3 (8.3) h. Fmor peaked in the same sample as Tmor. Range (median) of peak Fmor concentrations and time to last positive using a cutoff of 100 ng/m/for low and high doses were, respectively, 117–1160 (415) ng/mL, 1.2–10.1 (4.5) h and 150–2580 (1400) ng/mL, 2.3–29.1 (9.3) h. The range (median) of peak urine concentrations for 6-AM was 6.1–568 (124) ng/mL. In general, the first urine void had the peak 6-AM concentration and was the only specimen positive at a 10-ng/mL cutoff. As previously reported urine concentrations varied greatly between subjects and within subjects with time after dosing but were much more predictable when values were reported as amount of drug per unit of creatinine. The range (median) values for percent of heroin excreted into urine as Tmor was 12.8–88.5% (51.0).

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Subjects: Medical Toxicology ; Toxicology (Non-medical)

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