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

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.