Authors: Cone, Edward J.¹; Heit, Howard A.²; Caplan, Yale H.³; Gourlay, Douglas⁴

Source: Journal of Analytical Toxicology, Volume 30, Number 1, January/February 2006 , pp. 1-5(5)

Publisher: Preston Publications

Abstract:

Minor metabolic pathways in human subjects have been shown to exist for the conversion of codeine to hydrocodone but have not been reported for the metabolic conversion of morphine to hydromorphone. In this study, urine specimens were collected in an out-patient setting from 13 pain patients who were chronically treated with morphine and other opioids (methadone, oxycodone, and fentanyl). The chronic pain patients were chosen for study because they were treated with high-dose morphine and had no personal or family history of addiction. Results of the initial evaluation and follow up of these patients with random urine tests did not indicate opioid misuse. The specimens were analyzed by GC–MS for the presence of hydromorphone. The reporting limit for hydromorphone was 100 ng/mL. Ten of the 13 morphine-treated patients excreted hydromorphone in minor amounts ranging 120 to 1400 ng/mL. Concurrent morphine concentrations were exceedingly high in these 10 patients and frequently exceeded the upper limit of linearity (> 10,000 ng/mL) of the assay. The ratio of hydromorphone to morphine ranged from 0.015 to 0.024. Morphine concentrations in the three patients in which hydromorphone was not detected tended to be lower than those observed in other patients. For comparison, one additional patient was included in the study, who was prescribed both morphine and hydromorphone. Concentrations of hydromorphone in this patient were in the range of 3400–13,000 ng/mL, while concurrent morphine concentrations were in the range of 3200–6600 ng/mL. These data are highly suggestive that hydromorphone can be produced as a minor metabolite of morphine in humans. Although additional studies in more restricted settings are needed, it is recommended that interpretation of low urinary concentrations of hydromorphone in combination with high concentrations of morphine in morphine-treated pain patients should not be considered as conclusive evidence of hydromorphone misuse.

Document Type: Research article

Affiliations: 1: Johns Hopkins School of Medicine, Department of Psychiatry and Behavioral Sciences, Baltimore, Maryland 21224 2: 8316 Arlington Boulevard, Suite 232, Fairfax, Virginia, 22031 3: National Scientific Services, 3411 Phillips Drive, Baltimore, Maryland 21208 4: Pain and Chemical Dependency Division, Wasser Pain Management Centre, Mount Sinai Hospital, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

Publication date: 2006-01-01

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• The Journal of Analytical Toxicology (JAT), established in 1977 and published 9 times a year, is the international source covering a broad range of clinical, forensic, and industrial laboratory topics regarding the isolation, identification, and quantitation of potentially toxic substances.

  With an emphasis on practical application, JAT articles provide improved and novel techniques for use in clinical, forensic, workplace, sports testing (doping), and other toxicology laboratories. Articles describe newly developed methods in immunoassay testing, gas chromatography, liquid chromatography, mass spectrometry, atomic absorption spectrometry, solid and liquid phase extraction techniques, and other analytical approaches. Worldwide readership includes toxicologists, pathologists, chemists, clinicians, researchers, and educators working in medical examiner and law enforcement laboratories, hospitals, university and independent analytical laboratories, as well as the drug manufacturing industry.

  Each year in October, we publish a special issue from the Society of Forensic Toxicologists.

  JAT, as determined by ISI Citation Index, is one of the two most referenced international journals in forensic science.

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