Nitrosamine Impurities: Origin, Control and Regulatory Recommendations

The unexpected finding of presence of nitrosamine impurities, by USFDA and EMA in year 2018, in drugs such as Angiotensin-II Receptor Blockers (ARBs), Ranitidine, Nizatidine and Metformin, has triggered the need for a risk assessment strategy for evaluation and control of these probable human carcinogen - nitrosamine in pharmaceutical product that are at risk. This finding leads to voluntarily recall of products worldwide. The finding of nitrosamines in some types of drug products led FDA and other international regulators to conduct a detailed risk assessment of these impurities in APIs and drug products. Although nitrosamine impurities have been found in only some drug products, regulatory agencies recommended to extend risk analysis in other chemically synthesized APIs and drug products also.

Cyanotoxins Occurrence in Portugal: A New Report on Their Recent Multiplication

Historical reports show that in Portugal, cyanotoxins reports were mainly in the Center (cylindrospermopsins) and South (cylindrospermopsins, saxitoxins) regions of the country apart from the well distributed microcystins. Therefore, in our study, seven freshwater ecosystems located in the North and Center Regions of Portugal were screened between April and September of 2017 for the main cyanotoxins (microcystins, cylindrospermopsins, anatoxin-a, and saxitoxins) by a two methods approach that combined the application of molecular (PCR) and immunological (ELISA) assays. Results from our survey reveal that both methods revealed the presence of all main cyanotoxins. ELISA results showed that 48% of the samples were above (1.6–18.8 μg/L) the guideline value established for microcystins (1 μg/L), while in the remaining cyanotoxins, 33% of the samples were above (1.1–6.8 μg/L) the guideline value established for anatoxin–a (1 μg/L). Further, for saxitoxins, only one sample gave a value above (4.3 μg/L) the guideline (3 μg/L) and this corresponded to a North Region ecosystem. In the cytotoxin cylindrospermopsins, none of the samples were above the guideline established value (1 μg/L). This study will improve the risk assessment strategy in Portugal, as well as advance water quality and water management.