application): Workplace drug testing has now become fairly commonplace as a surveillance procedure in the American workplace. Hair testing has the potential to offer numerous advantages over urine and serum testing; some of those being 1) reduced cost; 2) convenience of sample storage and shipment; and 3) reduced psychological stress for the test subject. Despite these potential advantages, hair testing, however, has yet to become an accepted procedure due to unresolved issues as: 1) efficacy of drug extraction from hair; 2) differentiation between drugs contacted externally on the hair versus drugs ingested and deposited via the systemic circulation; 3) the effects of sweat and sebum on quantitation of hair drug levels; 4) correlation between ingested drug and distribution into hair; and 5) effects of pigment in hair deposition. The last issue may be the most important primarily because hair pigment in drug disposition has raised issues regarding differential sensitivity in and between various ethnic groups. In addition, gender bias may be significant when hair treatments such as dyes and salon treatments have the potential to remove or chemically alter or destroy deposited drugs. During the previous granting period, the investigators have accomplished the following objectives:(1) quantitation of hair growth rate via incorporating daily injections of rhodamine and measuring distance between fluorescent bands deposited in hair. Accessible water space was determined using a stage micrometer and equilibration of hairs with tritium oxide of known specific activity; (2) serum constituents as [C-14]urea, [Ca-45]calcium+2, [Cl-36]chloride- were quantitated and differences were noted in differentially pigmented hair; (3) highly covalently bound [S-35]cysteine was quantitated and a difference was noted in pigmented vs. less-pigmented hair. It was found that essentially no cysteine could be liberated on 24-hour extraction, consistent with possible covalent incorporation into hair matrix; (4) studies with fentanyl (as opposed to [H-3]-d-amphetamines and a benzoyl esterified amino alcohol, a model of cocaine) demonstrated that systemic delivery was not dose related, larger concentrations were extractable following external exposure, and "capping" of surface amino and hydroxyl groups resulted in significantly decreased, suggesting an interaction with hair chemical functionalities. Thus, a difference and a mechanism for fentanyl incorporation into hair via external and systemic route were semi-quantitatively determined. Studies were also accomplished with labeled cocaine, nicotine, and flunitrazepam; and (5) sodium sulfide digestion resulted in significantly greater recovery of base-stable drugs than NaOH.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA009545-05
Application #
6378611
Study Section
Special Emphasis Panel (ZRG1-SSS-Z (01))
Program Officer
Singh, Hari
Project Start
1997-05-15
Project End
2003-04-30
Budget Start
2001-05-01
Budget End
2002-04-30
Support Year
5
Fiscal Year
2001
Total Cost
$263,189
Indirect Cost
Name
University of Colorado Denver
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045
Dehn, D L; Claffey, D J; Duncan, M W et al. (2001) Nicotine and cotinine adducts of a melanin intermediate demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Chem Res Toxicol 14:275-9
Claffey, D J; Stout, P R; Ruth, J A (2001) 3H-nicotine, 3H-flunitrazepam, and 3H-cocaine incorporation into melanin: a model for the examination of drug-melanin interactions. J Anal Toxicol 25:607-11
Claffey, D J; Ruth, J A (2001) Amphetamine adducts of melanin intermediates demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Chem Res Toxicol 14:1339-44
Stout, P R; Ruth, J A (2000) Histologic localization of serum constituents, (45)Ca(2+), (36)Cl(-), [(14)C]urea, and [(35)S]cysteine in forming hair after systemic administration. Drug Metab Dispos 28:113-7
Claffey, D J; Stout, P R; Ruth, J A (2000) A comparison of sodium hydroxide and sodium sulfide digestion of mouse hair in the recovery of radioactivity following systemic administration of [3H]-nicotine and [3H]-flunitrazepam. J Anal Toxicol 24:54-8
Stout, P R; Ruth, J A (1999) Deposition of [3H]cocaine, [3H]nicotine, and [3H]flunitrazepam in mouse hair melanosomes after systemic administration. Drug Metab Dispos 27:731-5
Stout, P R; Claffey, D J; Ruth, J A (1998) Fentanyl in hair. Chemical factors involved in accumulation and retention of fentanyl in hair after external exposure or in vivo deposition. Drug Metab Dispos 26:689-700
Stout, P R; Ruth, J A (1998) Comparison of in vivo and in vitro deposition of rhodamine and fluorescein in hair. Drug Metab Dispos 26:943-8
Stout, P R; Dehn, D; Ruth, J A (1998) Deposition and retention of radiolabeled serum constituents in hair after systemic administration. Drug Metab Dispos 26:900-6