title: Determination of ibogaine and 12-hydroxy-ibogamine in plasma by gas chromatography-positive ion chemical ionization-mass spectrometry.
abstract: Ibogaine, an indolamine derivative, is currently being investigated as a potential agent in the treatment of stimulant and opiate addiction. We developed a rapid, sensitive, and specific method for the analysis of ibogaine and its putative active metabolite, 12-hydroxy-ibogamine (12-OH-ibogamine). This assay employs a one-step basic extraction with n-butyl chloride-acetonitrile (4:1), followed by derivatization of the metabolite using N-methyl-N-(tert-butyldimethylsilyl)-trifluoroacetamide. The derivatized extracts were analyzed by capillary gas chromatography-positive ion chemical ionization-mass spectrometry. The ions monitored were at m/z 311, 314, and 411, which correspond to the protonated molecules (MH+) for ibogaine, ibogaine-d3, and 12-OH-ibogamine.tert-butyldimethylsilyl, respectively. Linear standard curves were obtained over the concentration range of 1 0-1 000 ng/mL (average r2, 0.995 for ibogaine and 0.992 for 12-OH-ibogamine; n = 3). Limits of quantitation were 10 ng/mL. The interrun and intrarun coefficients of variation for the assay of ibogaine at 25, 100, and 300 ng/mL ranged from 2.9 to 8.8%. We also established the extraction and chromatographic conditions to monitor the 12-hydroxylated metabolite. A suitable internal standard was not yet obtained so the method could only provide semiquantitative information for 12-OH-ibogamine. Chemical stability studies of these analytes indicated that ibogaine and 12-OH-ibogamine were stable in a human plasma matrix at room temperature for a period of at least 1 week.
authors.affiliation: Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Alburges
authors.forename: R L
authors.initials: RL
authors.lastname: Foltz
authors.forename: D E
authors.initials: DE
authors.lastname: Moody
mesh_terms: D000081:Acetamides; D000097:Acetonitriles / Q000737:chemistry; D002073:Butanes / Q000737:chemistry; D002138:Calibration; D005463:Fluoroacetates; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006213:Hallucinogens / Q000097:blood*; D006801:Humans; D006900:Hydroxylation; D007050:Ibogaine / Q000031:analogs & derivatives* / Q000097:blood*; D017646:Organosilicon Compounds / Q000737:chemistry; D011786:Quality Control; D012015:Reference Standards; D013696:Temperature; D014269:Trifluoroacetic Acid / Q000737:chemistry
chemical_list: D000081:Acetamides; D000097:Acetonitriles; D002073:Butanes; D005463:Fluoroacetates; D006213:Hallucinogens; D017646:Organosilicon Compounds; D007050:Ibogaine; C059151:N-methyl-N-(tert-butyldimethylsilyl)trifluoroacetamide; C094385:noribogaine; D014269:Trifluoroacetic Acid; C032159:acetonitrile; C006854:butyl chloride