Performance Characteristics of Mass Spectrometry-Based Analytical Procedures for Quantitation of Nitrosamines in Pharmaceuticals: Insights from an Inter-laboratory Study.

With the discovery of carcinogenic nitrosamine impurities in pharmaceuticals in 2018 and subsequent regulatory requirements for risk assessment for nitrosamine formation during pharmaceutical manufacturing processes, storage or from contaminated supply chains, effective testing of nitrosamines has become essential to ensure the quality of drug substances and products. Mass spectrometry has been widely applied to detect and quantify trace amounts of nitrosamines in pharmaceuticals. As part of an effort by regulatory authorities to assess the measurement variation in the determination of nitrosamines, an inter-laboratory study was performed by the laboratories from six regulatory agencies with each of the participants using their own analytical procedures to determine the amounts of nitrosamines in a set of identical samples. The results demonstrated that accurate and precise quantitation of trace level nitrosamines can be achieved across multiple analytical procedures and provided insight into the performance characteristics of mass spectrometry-based analytical procedures in terms of accuracy, repeatability and reproducibility.

Fighting falsified medicines: The analytical approach.

Given the harm to human health, the fight against falsified medicines has become a priority issue that involves numerous actors. Analytical laboratories contribute by performing analyses to chemically characterise falsified samples and assess their hazards for patients. A wide range of techniques can be used to obtain individual information on the organic and inorganic composition, the presence of an active substance or impurities, or the crystalline arrangement of the formulation's compound. After a presentation of these individual techniques, this review puts forward a methodology to combine them. In order to illustrate this approach, examples from the scientific literature (products used for erectile dysfunction treatment, weight loss and malaria) are placed in the centre of the proposed methodology. Combining analytical techniques allows the analyst to conclude on the falsification of a sample, on its compliance in terms of pharmaceutical quality and finally on the safety for patients.