Identification, trace level quantification, and in silico assessment of potential genotoxic impurity in Famotidine.

Potential genotoxic impurities in medications are an increasing concern in the pharmaceutical industry and regulatory bodies because of the risk of human carcinogenesis. To prevent the emergence of these impurities, it is crucial to carefully examine not only the final product but also the intermediates and key starting material (KSM) used in drug synthesis. During the related substances analysis of KSM of Famotidine, an unknown impurity in the range of 0.5-1.0% was found prompting the need for isolation and characterization due to the possibility of its to infiltrate into the final product. In this study, the impurity was isolated and characterized as 5-(2-chloroethyl)-3,3-dimethyl-3,4-dihydro-2H-1,2,4,6-thiatriazine 1,1-dioxide using multiple instrumental analysis, uncovering a structural alert that raises concern. Considering the potential impact of impurity on human health, an in silico genotoxicity assessment was established using Derek and Sarah tool in accordance with ICH M7 guideline. Furthermore, molecular docking and molecular dynamics simulation were performed to evaluate the specific interaction of the impurity with DNA. The findings reveal consistent interaction of the impurity with the dG-rich region of the DNA duplex and binding at the minor groove. Both in silico prediction and molecular dynamic study confirmed the genotoxic character of the impurity. The newly discovered impurity in famotidine has not been reported previously, and there is currently no analytical method available for its identification and control. A highly sensitive HPLC-UV method was developed and validated in accordance with ICH requirements, enabling quantification of the impurity at trace level in famotidine ensuring its safe release.

Rare Presentation of a Patient with Cardiac Arrest Due to Cerebral Fat Embolization Following Polytrauma.

Cerebral fat embolism (CFE) syndrome is a known complication that can occur following polytrauma, particularly in cases involving fractures of long bones, but cardiac arrest is a rare presentation following cerebral fat embolization.1 Our patient met with a road traffic accident (RTA), sustaining multiple long bones injuries with hypovolemic shock. After 10 hours of admission and achieving hemodynamic stability, the patient developed cerebral fat embolization. He developed sudden cardiac arrest and was resuscitated. We instituted ventilator support, inotropic infusion, antibiotics, and intravenous (IV) fluids. Our patient regained consciousness without neurological deficit over a period of 10 days and underwent surgery for all three major fractures with due precautions. The patient was discharged after 3 weeks of treatment from the hospital. How to cite this article: Rathod N, Rathod V, Parikh B, et al. Rare Presentation of a Patient with Cardiac Arrest Due to Cerebral Fat Embolization Following Polytrauma. J Assoc Physicians India 2023;71(11):89-93.