SOFT 2004 Meeting Abstracts - Society of Forensic Toxicologists

M28
DOSE-RELATED DISTRIBUTION OF CODEINE, COCAINE AND METABOLITES INTO
HUMAN HAIR FOLLOWING CONTROLLED ORAL CODEINE AND SUBCUTANEOUS
COCAINE ADMINISTRATION
Karl B. Scheidweiler l *, Edward J. Cone 2 , Eric T. Moolchan l and Marilyn A. Huestis l : 1 National Institute
on Drug Abuse, 5500 Nathan Shock Drive, Baltimore, MD: 2 ConeChem Research, LLC, Severna Park,
MD
Ten volunteers with histories of cocaine and opiate use consented to reside on a secure clinical research
ward at the Intramural Research Program, National Institutes on Drug Abuse, National Institutes of Health
to participate in a ten-week controlled cocaine and opiate administration study. This Intramural Research
Board approved study was designed to investigate excretion of opiates, cocaine and metabolites into hair
following multiple subcutaneous (s.c.) cocaine hydrochloride and oral (p.o.) codeine sulfate doses. The
first three weeks of the study comprised the drug washout phase. During the low dose drug administration
week (week 4) 75 mg/ 70 kg cocaine, s.c. and 60 mg/ 70 kg codeine, p.o. doses were administered on
alternating days for a total of three doses for each drug. The high dose drug administration week began on
week 8 during which, subjects received three doses of 150 mg/ 70 kg cocaine, s.c. and 120 mgi 70 kg
codeine, p.o. on alternating days. An electric razor was used to collect hair at the end of each week during
the study. Drugs were extracted from pulverized hair via methanolic sonication and extracts were analyzed
for cocaine, norcocaine, benzoyl ecgonine (BE), ecgonine methyl ester (EME), cocaethylene (CE), codeine,
norcodeine, morphine and 6-acetylmorphine (6-AM) via liquid chromatography-atmospheric pressure
chemical ionization tandem mass spectrometry. Limits of quantitation (LOQ) for cocaine and metabolites
were 17 pg/mg, except for EME (50 pg/mg). Opiate LOQs were 83 pg/mg, except for norcodeine (240
pgimg).
Maximum cocaine and metabolite concentrations (Cmax) were generally measured in hair samples
collected two weeks after drug dosing (range: one to three weeks). Average cocaine and metabolite
Cmax's (::I: standard error of the mean) measured in hair reflecting the low dose cocaine week
administrations were 2,997 ::I: 619, 314 ::I: 51, 187 ::I: 27, 84 ::I: 21 pg/mg of cocaine, BE, EME and
norcocaine, respectively. Mean cocaine and metabolite Cmax's measured reflecting the high dose cocaine
week administrations were 6,419::1: 1,698,708::1: 163,425::1: 65, 218::1: 46 pg/mg of cocaine, BE, EME, and
norcocaine, respectively. Norcocaine did not exceed the LOQ after the low cocaine dosing in one often
individuals. In all other cases, cocaine and metabolites exceeded the LOQ after low and high cocaine
dosings. Comparison of cocaine and metabolite hair Cmax's that occurred after low and high dose cocaine
weeks revealed significant dose-relationships and were significantly different from hair concentrations at
the conclusion ofthe washout phase as evaluated using Wilcoxon signed rank test (p