A sensitive method for determining levels of [−]-2,5,-dimethoxy-4-methylamphetamine in the brain tissue

• Published in: Journal of pharmacological and toxicological methods Vol. 46; no. 1; pp. 37 - 43
• Main Authors: Eckler, J.R, Greizerstein, H, Rabin, R.A, Winter, J.C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2001
• Subjects: [−]-DOM; Animals; Brain; Brain - metabolism; Dextroamphetamine - pharmacokinetics; DOM 2,5-Dimethoxy-4-Methylamphetamine - pharmacokinetics; Dose-Response Relationship, Drug; Gas chromatography; Gas Chromatography-Mass Spectrometry; Hallucinogens - pharmacokinetics; Male; Mass spectrometry; Methods; Rat; Rats; Rats, Inbred F344; Reproducibility of Results; Brain; Gas chromatography; Rat; [−]-DOM; Mass spectrometry; Methods
• ISSN: 1056-8719; 1873-488X
• DOI: 10.1016/S1056-8719(02)00159-4

Introduction: Indolamine and phenethylamine hallucinogens are drugs of abuse and, as well, mimic some aspects of idiopathic psychosis. To assist in investigating the mechanisms of action of (−)2,5-dimethoxy-4-methylamphetamine ([−]-DOM), a member of the phenethylamine class of serotonergic hallucinogens, a sensitive and precise method for determining its levels in the brain tissue is required. Methods: We now describe a method for determining nanogram quantities of [−]-DOM in the rat brain tissue using d-amphetamine as an internal standard. The method employs solvent extraction with toluene and derivatization with trifluoroacetic acid anhydride (TFAA) followed by analysis using gas chromatography–mass spectrometry (GS–MS) in the selective ion monitoring (SIM) mode. Results: With SIM detection, our overall recoveries were greater than 90%. The method was reliable in terms of within-day and between-day precision, accuracy, and linearity. The procedure was applied to animal subjects to determine the in vivo [−]-DOM brain levels following intraperitoneal (ip) administration. Our findings indicate that peak levels of [−]-DOM do not coincide with the 75-min pretreatment time established by drug-induced stimulus control. Discussion: This study demonstrates a sensitive and precise analytical method for the determination of [−]-DOM levels in the rat brain following systemic administration of behaviorally relevant doses.