Abdelwahab Nada S, Edrees Fadwa H, Alsaadi Mohammed T, Amin Noha H, Saad Ahmed S
Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Beni-Suef University 62514 Beni-Suef Egypt
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University (NUB) 62511 Beni-Suef Egypt
RSC Adv. 2020 Oct 9;10(61):37439-37448. doi: 10.1039/d0ra06147f. eCollection 2020 Oct 7.
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.
《英国药典》（BP）报告称，具有致癌性和肝毒性的二苯甲酮（BZP）是茶苯海明（DMH）的一种杂质。另一方面，据报道桂利嗪（CIN）有五种杂质（A - E）。对CIN杂质的毒性特征进行了研究，数据显示杂质A [1 - （二苯甲基）哌嗪]（DPP）是CIN中毒性最强的杂质，因此在本研究中被选用。建立了薄层色谱 - 密度测定法用于分离并同时定量测定DMH、CIN及其有毒杂质。在所提出的方法中，使用正己烷∶乙醇∶丙酮∶冰醋酸（体积比为7∶3∶0.7∶0.5），并在225 nm处进行紫外扫描。按照国际人用药品注册技术协调会（ICH）指南进行了方法验证，DMH、CIN、BZP和DPP每带的线性范围分别为0.2 - 4、0.5 - 5、0.1 - 2.0和0.05 - 2.2 μg。将该方法应用于药物制剂时，未观察到来自添加剂的干扰。使用分析生态尺度评估了该方法的绿色度，结果表明所开发方法对环境的负面影响较小。
