Codeine concentration in hair after oral administration is dependent on melanin content

Background: Analysis of drugs in hair has been used on a qualitative basis to estimate earlier exposure to drugs. Clinical applications are rare becau se of the lack of dose-response relationships in the studies performed to d ate, and questions remain regarding the mechanisms of drug incorporation in to 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 incorporat ed. Methods: Nine human subjects were given codeine as a single oral dose, and plasma codeine concentrations were determined for 24 h, using gas chromatog raphy-mass spectrometry. Hair samples were obtained weekly for a month. Tot al melanin, eumelanin, and codeine were measured quantitatively in hair sam ples by spectrophotometry, HPLC, and gas chromatography-mass spectrometry, respectively. Results: There was an exponential relationship between codeine and melanin concentrations in hair, (r(2) = 0.95 with total melanin and r(2) = 0.83 wit h eumelanin). After normalizing the results by the area under the curve for codeine in plasma, we obtained r(2) = 0.86 for codeine vs total melanin an d r(2) = 0.90 vs eumelanin. Conclusions: Our results stress the importance of melanin determination whe n measuring drugs in hair. We postulate that analysis of drug concentration in hair may be worthwhile in the monitoring of drug compliance if the resu lts are normalized for melanin content. (C) 1999 American Association for C linical Chemistry.