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Codeine Concentration in Hair after Oral Administration Is Dependent on Melanin Content

¹ National Board of Forensic Medicine, Department of Forensic Chemistry, University Hospital, 581 85 Linköping, Sweden.

² Department of Clinical Chemistry, Faculty of Health, University of Linköping, 581 85 Linköping, Sweden.
^a Author for correspondence. Fax 46-13-10-48-75; e-mail robert.kronstrand{at}rk.rmv.se

Background: Analysis of drugs in hair has been used on a qualitative basis to estimate earlier exposure to drugs. Clinical applications are rare because of the lack of dose–response relationships in the studies performed to date, and questions remain regarding the mechanisms of drug incorporation into hair. Several human studies have shown differences in drug accumulation between pigmented and nonpigmented hair. However, the melanin concentration in hair was not determined and correlated to the amount of drug incorporated.

Methods: Nine human subjects were given codeine as a single oral dose, and plasma codeine concentrations were determined for 24 h, using gas chromatography–mass spectrometry. Hair samples were obtained weekly for a month. Total melanin, eumelanin, and codeine were measured quantitatively in hair samples by spectrophotometry, HPLC, and gas chromatography–mass spectrometry, respectively.

Results: There was an exponential relationship between codeine and melanin concentrations in hair, (r² = 0.95 with total melanin and r² = 0.83 with eumelanin). After normalizing the results by the area under the curve for codeine in plasma, we obtained r² = 0.86 for codeine vs total melanin and r² = 0.90 vs eumelanin.

Conclusions: Our results stress the importance of melanin determination when measuring drugs in hair. We postulate that analysis of drug concentration in hair may be worthwhile in the monitoring of drug compliance if the results are normalized for melanin content.

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