Marcelo Secatto*, Murilo Massoni and Vincenzo De Sio,
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引用次数: 0
Abstract
Since the International Agency for Research on Cancer (IARC) classified most of N-nitrosamines as potentially carcinogenic or mutagenic harmful agents, in addition to the recent worldwide episode where the presence of these substances was identified on medicines derived from sartans (e.g., Valsartan) and other active pharmaceutical ingredients (APIs) (e.g., Ranitidine, Nizatidine, and Metformin), regulatory agencies such as FDA, EMA, and ANVISA became concerned about the needs of pharmaceutical companies for evaluating their products and their respective manufacturing steps to ensure safety and quality. As the technical and regulatory approach to the subject advanced, it was established that the presence of these substances could be originated from different steps, both from API and finished product processes. Thus, several multidisciplinary committees were formed to discuss effective strategies to assess the qualitative and quantitative risk of contamination and formation of nitrosamines on products. In perspective on the production chain of active pharmaceutical ingredients, the aim of this study is to show the relevant results obtained from the risk assessment of nitrosamines for the API Temozolomide industrial process, produced by the pharmaceutical company Cristália. The study focused on realizing a complete and robust risk assessment from the stages of synthesis and equipment evaluation to packaging and stability condition, applying in silico analyses verified by confirmatory analytical test through gas chromatography (GC) methodology.
期刊介绍：
The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.
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