Underberg W J
J Pharm Sci. 1978 Aug;67(8):1133-8. doi: 10.1002/jps.2600670828.
The kinetics of the thermal degradation of promethazine in an acidic medium under various conditions were investigated. The degradation of promethazine and the formation of some degradation products were studied under aerobic and anaerobic conditions. The influence of pH, metal ions such as copper(II) and iron (III), and antioxidants was investigated. In an oxygen-saturated medium, promethazine generally followed first-order kinetics. Increasing the pH increased the degradation rate to a limiting value at pH 5. Addition copper (II) increased the degradation rate over the whole process, while iron (III) caused an increase for only a short time. Ascorbic acid sometimes increased the degradation rate, while higher concentrations of hydroquinone also accelerated the degradation. Pyrosulfite did not have any influence. Under anaerobic conditions, promethazine degraded only in the presence of copper (II) and iorn (III) ions. As a result of the studies on the qualitative and quantitative aspects of the oxidation process, a mechanism for the oxidative degradation of promethazine is suggested. Promethazine 5-oxide and a number of degradation products without intact side chains are formed via a semiquinone free radical. The influence of several factors on the degradation process is discussed.
研究了在不同条件下，酸性介质中异丙嗪的热降解动力学。在有氧和无氧条件下，研究了异丙嗪的降解以及一些降解产物的形成。考察了pH值、铜（II）和铁（III）等金属离子以及抗氧化剂的影响。在氧饱和介质中，异丙嗪一般遵循一级动力学。提高pH值会使降解速率增加，在pH 5时达到极限值。添加铜（II）会使整个过程的降解速率增加，而铁（III）只会在短时间内导致降解速率增加。抗坏血酸有时会增加降解速率，而较高浓度的对苯二酚也会加速降解。焦亚硫酸盐没有任何影响。在无氧条件下，异丙嗪仅在铜（II）和铁（III）离子存在时降解。通过对氧化过程的定性和定量研究，提出了异丙嗪氧化降解的机制。异丙嗪5-氧化物和一些没有完整侧链的降解产物是通过半醌自由基形成的。讨论了几个因素对降解过程的影响。
