Mazzei M, Roma G, Balbi A, Sottofattori E, Robbiano L
Istituto di Scienze Farmaceutiche, Università di Genova, Italy.
Farmaco Sci. 1988 Jun;43(6):523-38.
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.
由于乐果（DMP）亚硝化混合物表现出的遗传毒性效应，在广泛的试剂浓度、摩尔比、反应时间和pH值范围内，研究了盐酸乐果与亚硝酸钠在37℃酸性水溶液中的相互作用。实际上，根据操作条件，有可能检测到不同量的2,6 - 二甲氧基 - 1,4 - 苯醌（DMBQ），一种具有高度遗传毒性的化合物，但未检测到N - 亚硝基衍生物。当DMP和NaNO₂的浓酸性溶液（摩尔比1:1.9）在pH 3.0 - 4.0下反应时，DMP转化为DMBQ的转化率最高（1小时后为50 - 60%，具体取决于pH条件）。当盐酸乐果和NaNO₂（摩尔比1:0.95）在更稀的溶液中于pH 3.5下反应以模拟胃部条件时，20分钟后DMP转化为DMBQ的转化率约为3%。向试剂中添加适量的抗坏血酸可以防止DMP的分解。
