title: Salsolinol and isosalsolinol: condensation products of acetaldehyde and dopamine. Separation of their enantiomers in the presence of a large excess of dopamine.
abstract: Dopamine (DA) condenses, at least in vitro, with acetaldehyde, the primary metabolite of ethanol, to form the regioisomers salsolinol (SAL) and isosalsolinol (isoSAL). An alternative in vivo route to SAL, requiring a decarboxylation step, has been suggested via condensation of DA with pyruvic acid. SAL has been proposed as a mediator of the rewarding effects of ethanol in the brain. We have now shown by HPLC, nuclear magnetic resonance (NMR) and mass spectrometry (MS) that the commercially available SAL contains about 10% of isoSAL, whose biological activity is unknown. If SAL is indeed the biologically active metabolite, rather than isoSAL, it is also unknown whether the rewarding molecule is (S)- or (R)-SAL. We have developed methodologies for the quantitative determination of DA, SAL and isoSAL using ion-pair reversed-phase HPLC, and for the separation of DA from (S)- and (R)-SAL and an isoSAL enantiomer on a β-cyclodextrin-modified column, in both cases with electrochemical detection. A significant advance over earlier methods was achieved for the analysis of (S)- and (R)-SAL in the presence of a large excess of DA (100:1 DA-SAL ratio), as expected to occur in vivo, by suppressing the DA peak by selective derivatization with 2,3-naphthalenedicarboxaldehyde into a molecule that is electrochemically silent at the electrode potential used. The methodologies developed will allow the separation and determination of the pharmacological activity of these two products of condensation of acetaldehyde with DA. Further, the techniques for (S)- and (R)-SAL separation at a high DA:SA ratio will allow the existence of a putative (R)-SAL synthase to be determined and, if it exists, its role in alcoholism.
authors.affiliation: Department of Toxicological and Pharmacological Chemistry, Faculty of Chemical and Pharmaceutical Sciences, Santiago, Chile.
authors.forename: María de Los Ángeles
authors.initials: MA
authors.lastname: Juricic
authors.forename: Pablo A
authors.initials: PA
authors.lastname: Berríos-Cárcamo
authors.forename: Mónica L
authors.initials: ML
authors.lastname: Acevedo
authors.forename: Yedy
authors.initials: Y
authors.lastname: Israel
authors.forename: Iriux
authors.initials: I
authors.lastname: Almodóvar
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Cassels
mesh_terms: D000079:Acetaldehyde / Q000737:chemistry*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D056148:Chromatography, Reverse-Phase / Q000592:standards; D004298:Dopamine / Q000737:chemistry*; D007536:Isomerism; D007546:Isoquinolines / Q000737:chemistry / Q000302:isolation & purification*; D013058:Mass Spectrometry; D009281:Naphthalenes / Q000737:chemistry
chemical_list: D007546:Isoquinolines; D009281:Naphthalenes; C027717:2,3-naphthalenedicarboxaldehyde; C036617:salsolinol; D000079:Acetaldehyde; D004298:Dopamine