A study into the rate of incorporation of eight benzodiazepines into rat hair.
The incorporation of eight benzodiazepines (chlordiazepoxide, diazepam, estazolam, flunitrazepam, flurazepam, medazepam, oxazepam and triazolam) into rat hair was investigated by HPLC and GC-MS. Each of the benzodiazepines was injected daily into three Dark Agouti (DA) rats for 10 days at 10mg/kg. The back hair of the rats was removed by shaving prior to the first injection and again on the 28th day after the initial administration. To investigate optimum extraction conditions, 10mg aliquots of rat hair incorporated with diazepam, flurazepam or medazepam were extracted by seven different methods (Proteinase K, methanol-ammonia, methanol-trifluoroacetic acid, Soerensens buffer, 1M NaOH, beta-glucuronidase/arylsulfatase, Biopurase). The method found to yield the highest recoveries, for all three drugs, was the acidic methanol extraction. Using this extraction procedure, the incorporation rates (ICR: the ratio of the hair concentration to the plasma AUC) of eight benzodiazepines into rat hair were investigated. The ICRs ranged from 0.002 (flunitrazepam) to 0.049 (flurazepam). The major metabolites of flurazepam were investigated in rat hair. The mean hair concentrations of desalkylflurazepam and 2-hydroxyethylflurazepam were 3.31 and 0.05 ng/mg, respectively, which are 24 and 0.36% of the parent compound in hair.
Scott
Karen S
KS
Department of Forensic Science and Chemistry, Anglia Polytechnic University, East Road, Cambridge CB1 1PT, UK. k.s.scott@apu.ac.uk
Nakahara
Yuji
Y
D000818:Animals; D001569:Benzodiazepines / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006197:Hair / Q000378:metabolism*; D008297:Male; D051381:Rats
D001569:Benzodiazepines