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Title	Mechanisms of phencyclidine incorporation into hair
Publication Type	dissertation
School or College	College of Pharmacy
Department	Pharmacology & Toxicology
Author	Slawson, Matthew Howard
Date	1997
Description	The incorporation of drugs into hair is an area of increasing scientific interest. The purpose of this project was to investigate the mechanisms of incorporation and retention of xenobiotics in the hair of laboratory rodents using phencyclidine (PCP) as a model compound. The incorporation of PCP into the pigmented and nonpigmented hair of Long-Evans (LE) rats increased as the dose of PCP was increased. There was a 30-fold greater incorporation into pigmented hair compared to nonpigmented hair from the same animal. The hair concentration (ng/mg) of PCP was not changed in spite of different amounts of hair collected from distinct dosing intervals in the same group of LBNFI rats. A single dose of PCP was detected in terminal segments of collected rat hair. However, it was possible to localize the discrete band of PCP to within only 50% of the hair length. The potential for PCP to be retained within hair via an ionic mechanism was investigated by altering the ionic equilibrium of PCP with buffers of varying pH in an attempt to displace PCP from binding sites within the hair. Increasing the pH of the extraction buffer, increased the amounts of PCP removed from pigmented LE rat hair. The same PCP extraction pattern was not seen for nonpigmented LE hair. Phenobarbital showed no pH-dependent extraction from pigmented LE rat hair. These data were further supported by in vitro incubations with sepia melanin. These results suggested that noncationic drug forms (i.e., phenobarbital) have a lesser capacity for binding with melanin, both in hair and in vitro. Rodent hair with eumelanin as the principle pigment incorporated more PCP than rodent hair with either no melanin or pheomelanin as the principle pigment. The data from this dissertation have demonstrated that PCP is a useful model drug for studying the mechanisms of drug incorporation and retention in hair. Results indicate that PCP is retained within pigmented hair via an ionic interaction with eumelanin. Eumelanin appears to playa larger role than pheomelanin in incorporating PCP into hair.
Type	Text
Publisher	University of Utah
Subject	Hair; effect of drugs on hair; analysis phencyclidine form/ genre electronic books
Dissertation Name	Doctor of Philosophy
Language	eng
Rights Management	© Matthew Howard Slawson
Format	application/pdf
Format Medium	applocation/pdf
ARK	ark:/87278/s6k7dp11
Setname	ir_etd
ID	2550650
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6k7dp11

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Title	Page 100
Format	application/pdf
Setname	ir_etd
ID	2550750
OCR Text	Show 91 29. C. Offldani, A. Carnevale, and M. Chiarotti: Drugs in hair: a new extraction procedure. Forensic Sci. Int. 41, 35-39 (1989). 30. Y. Nakahara and R. Kikura: Hair analysis for drugs of abuse. VII. The incorporation rates of cocaine, benzoylecgonine and ecgonine methyl ester into rat hair and hydrolysis of cocaine in rat hair. Arch. Toxicol. 681, 54-59 (1994). 31. Y. Nakahara, T. Ochiai, and R. Kikura: Hair analysis for drugs of abuse. V. The facility in incorporation of cocaine into hair over its major metabolites, benzoylecgonine and ecgonine methyl ester. Arch. Toxicol. 66, 446-449 (1992). 32. M. R. Moller, P. Fey, and S. Rimbach: Identification and Quantitation of Cocaine and Its Metabolites, Benzoylecgonine and Ecgonine Methyl Ester, in Hair of Bolivian Coca Chewers by Gas Chromatography/Mass Spectrometry. J. Anal. Toxicol. 16,291- 296 (1992). 33. M. R. Moeller: Drug Detection in Hair by Chromatographic Procedures. J. Chromatogr. 580, 125-134 (1992). 34. M. Michalodimitrakis: Detection of cocaine in rats from analysis of hair. Med. Sci. Law 27, 13-5 (1987). 35. R. Martz, B. Donnelly, D. Fetterolf, L. Lasswell, G. W. Hime, and W. L. Hearn: The Use of Hair Analysis to Document a Cocaine Overdose Following a Sustained Survival Period Before Death. J. Anal. Toxicol. 15, 279-281 (1991). 36. R. M. Martz: The identification of cocaine in hair by GC/MS and MSfMS. Crime Lab. Dig. 15, 67-73 (1988). 37. F. Martinez, T. S. Poet, R. Pillai, J. Erickson, A. L. Estrada, and R. R. Watson: Cocaine Metabolite (Benzoylecgonine) in Hair and Urine of Drug Users. J. Anal. Toxicol. 17, 138-142 (1993). 38. J. Klein, R. Forman, C. Eliopoulos, and G. Koren: A method for simultaneous measurement of cocaine and nicotine in neonatal hair. Ther. Drug Monit. 16, 67 -70 (1994). 39. K. Janzen: Concerning Norcocaine, Ethylbenzoylecgonine, and the Identification of Cocaine Use in Human Hair. I. Anal. Toxicol. 16, 402 (1992). 40. G. L. Henderson, M. R. Harkey, C. Zhou, and R. T. Jones: Cocaine and metabolite concentrations in the hair of South American coca chewers. J. Anal. Toxicol. 16, 199201 (1992). 41. M. R. Harkey, G. L. Henderson, and C. H. Zhou: Simultaneous Quantitation of Cocaine and Its Major Metabolites in Human Hair by Gas Chromatography/Chemical Ionization Mass Spectrometry. l. Anal. Toxicol. 15, 260-265 (1991). 42. K. Graham, G. Koren, 1. Klein, J. Schneiderman, and M. Greenwald: Determination of gestational cocaine exposure by hair analysis. lAMA 262,3328-3330 (1989). 43. D. Fritch, Y. Groce, and F. Rieders: Cocaine and Some of Its Products in Hair by RIA and GCIMS. 1. Anal. Toxico!. 112-114 16, (1992).
Reference URL	https://collections.lib.utah.edu/ark:/87278/s6k7dp11/2550750