title: Formation of 2,6-dimethoxy-1,4-benzoquinone, a highly genotoxic compound, from the reaction of sodium nitrite with the sympathomimetic drug dimethophrine in acidic aqueous solution.
abstract: Because of the genotoxic effects shown by Dimethophrine (DMP) nitrosation mixtures, the interaction between DMP hydrochloride and sodium nitrite in acidic aqueous solution at 37 degrees was investigated in a wide range of reagent concentrations and molar ratios, reaction times and pH values. Actually, depending on the operating conditions, it was possible to detect variable amounts of 2,6-dimethoxy-1,4-benzoquinone (DMBQ), a highly genotoxic compound, but no N-nitrosoderivative. The highest conversion of DMP into DMBQ was obtained when concentrated acidic solutions of DMP and NaNO2 (molar ratio 1:1.9) reacted at pH 3.0-4.0 (50-60% after 1 hour, depending on the pH conditions). When DMP hydrochloride and NaNO2 (molar ratio 1:0.95) were allowed to react at pH 3.5 in a more diluted solution, to mimic gastric conditions, the conversion of DMP into DMBQ after 20 min was about 3%. The breakdown of DMP can be prevented by adding suitable amounts of ascorbic acid to the reagents.
authors.affiliation: Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mazzei
authors.forename: G
authors.initials: G
authors.lastname: Roma
authors.forename: A
authors.initials: A
authors.lastname: Balbi
authors.forename: E
authors.initials: E
authors.lastname: Sottofattori
authors.forename: L
authors.initials: L
authors.lastname: Robbiano
mesh_terms: D016227:Benzoquinones; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D004983:Ethanolamines / Q000032:analysis*; D009153:Mutagens / Q000138:chemical synthesis*; D009573:Nitrites / Q000032:analysis*; D011809:Quinones / Q000138:chemical synthesis* / Q000633:toxicity; D012977:Sodium Nitrite / Q000032:analysis*; D013055:Spectrophotometry, Infrared; D013566:Sympathomimetics / Q000032:analysis*
chemical_list: D016227:Benzoquinones; D004983:Ethanolamines; D009153:Mutagens; D009573:Nitrites; D011809:Quinones; D013566:Sympathomimetics; C030511:2,6-dimethoxy-1,4-benzoquinone; C100197:dimethophrine; D012977:Sodium Nitrite