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.
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.
Mazzei
M
M
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Roma
G
G
Balbi
A
A
Sottofattori
E
E
Robbiano
L
L
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*
D016227:Benzoquinones; D004983:Ethanolamines; D009153:Mutagens; D009573:Nitrites; D011809:Quinones; D013566:Sympathomimetics; C030511:2,6-dimethoxy-1,4-benzoquinone; C100197:dimethophrine; D012977:Sodium Nitrite