Simultaneous estimation of dimenhydrinate, cinnarizine and their toxic impurities benzophenone and diphenylmethylpiperazine; toxicity profiling of impurities.

The British Pharmacopeia (BP) reported that the carcinogenic and hepatotoxic, benzophenone (BZP) is a dimenhydrinate (DMH) impurity. On the other hand, cinnarizine (CIN) is reported to have five impurities (A-E). The toxicity profile of CIN impurities was studied and the data revealed that impurity A [1-(diphenylmethyl)piperazine] (DPP) was the most toxic CIN impurity, and hence it was selected during this work. TLC-densitometric method was developed for separation and simultaneous quantitation of DMH, CIN and their toxic impurities. In the proposed method hexane : ethanol : acetone : glacial acetic acid (7 : 3 : 0.7 : 0.5, by volume) with UV scanning at 225 nm were used. Method validation was carried out according to ICH guidelines and linearity was achieved in the range 0.2-4, 0.5-5, 0.1-2.0, and 0.05-2.2 μg per band for DMH, CIN, BZP and DPP, respectively. On the application of the method to pharmaceutical formulation, no interference from additives was observed. The greenness of the method was evaluated using the analytical eco-scale and the results revealed the low negative environmental impact of the developed method.