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Published:
Journal of Analytical Toxicology,
ISSN 0146-4760,
Volume 25, Number 7, October, pp. 607-611
3H-Nicotine, 3H-Flunitrazepam, and
3H-Cocaine Incorporation Into Melanin: A Model for the Examination
of Drug–Melanin Interactions*
David J. Claffey, Peter R. Stout, and James A. Ruth
University of Colorado Health Sciences Center, Molecular Toxicology and Environmental
Health Sciences, 4200 East Ninth Ave. Box C238, Denver, Colorado 80262
To explore drug–melanin interactions, we examined the in
vitro tyrosinase-mediated formation of melanin from tyrosine in the presence
of the 3H-cocaine (3H-COC), 3H-flunitrazepam (3H-FLU), and 3H-nicotine (3H-NIC)
at 10–100,000 ng/mL. Polymerization in the presence of 10 or 100 ng/mL
of each drug resulted in almost complete drug incorporation into the melanin
pellet. Only 12% (3H-NIC) to 28% (3H-FLU) of the pellet-associated radioactivity
could be released upon treatment with 6M HCl. At 1000–100,000 ng/mL, between
20 and 50% of label became melanin-associated. In each case a significant percentage
of melanin-associated radioactivity was resistant to treatment with 6M HCl.
Nicotine-associated radioactivity in the polymer was subject to much greater
quenching than was 3H-COC or 3H-FLU, suggesting a much tighter association with
the melanin. The subsequent demonstration of a covalent adduct of a melanin
intermediate and nicotine has demonstrated the utility of this polymerization
system as a model for further chemical characterization of drug–melanin
interactions.
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