The accumulation and disappearance of cocaine and benzoylecgonine in rat hair following prolonged administration of cocaine.
Hair samples were obtained at various time periods from male Sprague-Dawley rats following the injection of cocaine hydrochloride in doses of 5, 10, and 20 mg/kg, ip, for 28 days. Hair samples were also taken continually after the dosing was stopped until the presence of cocaine and benzoylecgonine were no longer detected in hair. Cocaine and benzoylecgonine in hair and plasma were analyzed by gas chromatography/mass spectrometry. Both cocaine and benzoylecgonine were found in hair samples 4 days after the initiation of cocaine administration. When cocaine dosing was stopped after 28 days, approximately 25 to 30 days were required for cocaine and benzoylecgonine to disappear from rat hair in the group of animals that received the highest dose of cocaine. The disappearance of cocaine and benzoylecgonine followed first-order kinetics. The mean rate constant and mean half-life for cocaine disappearance from hair were 0.212 +/- 0.005 day-1 and 3.31 +/- 0.09 days, respectively, and the mean rate constant and mean half-life for benzoylecgonine disappearance from hair were 0.098 +/- 0.006 day-1 and 6.90 +/- 0.28 days, respectively. The mean plasma concentrations of cocaine on Day 25 for the 5, 10, and 20 mg/kg doses of cocaine were 508 +/- 42, 852 +/- 95, and 2027 +/- 75 ng/mL, respectively, and the mean plasma benzoylecgonine levels for the 5, 10, and 20 mg/kg doses of cocaine were 49.9 +/- 7.0, 103.3 +/- 9.3, and 191.0 +/- 16.0 ng/mL, respectively. There was a positive correlation between the doses of cocaine hydrochloride administered and the plasma levels of both cocaine and benzoylecgonine. This study showed that cocaine and benzoylecgonine can be measured in rat hair following the administration of cocaine and that it was possible to correlate the concentrations of cocaine and benzoylecgonine found in hair with the doses of cocaine that were administered.
Ferko
A P
AP
Department of Pharmacology, Hahnemann University, School of Medicine, Philadelphia, Pennsylvania 19102.
Barbieri
E J
EJ
DiGregorio
G J
GJ
Ruch
E K
EK
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D006197:Hair / Q000378:metabolism*; D006207:Half-Life; D007274:Injections, Intraperitoneal; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
C005618:benzoylecgonine; D003042:Cocaine