Navigating the complexities in characterization of NDSRIs using advanced analytical techniques-Pub

Confirmatory Testing & Analytical Challenges
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https://jpharmsci.org/article/S0022-3549(26)00063-8/abstract

Abstract

The accurate detection and quantification of nitrosamine drug substance related impurities (NDSRIs) requires validated analytical techniques. However, the availability of standards for validation is still evolving due to the structural complexity of these impurities. Thus, standards often need to be synthesized in-house and characterized to confirm identity and purity. In some cases, the synthesis of NDSRIs may follow alternative reaction pathways leading to the formation of compounds other than N-nitrosated derivatives, potentially resulting in the generation of new impurities. Among various analytical techniques, liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy stand out for characterization of NDSRIs due to their ability to provide detailed structural information and distinguish between different isomers. In this study, the application of LC-MS and NMR spectroscopy in the characterization of NDSRIs was explored and the identification of three new process related impurities formed during the synthesis of NDSRIs are discussed. Structural differentiation of the C- and N- nitroso analogs is difficult solely using MS techniques due to the identical molecular mass, thus the significance of employing ¹⁵N two-dimensional NMR spectroscopy for investigating impurity formation during structural characterization is emphasized here. This study shows that advanced analytical techniques help achieve more accurate identification of NDSRIs, which in turn ensures that pharmaceutical products meet high quality standards.

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very interesting…and it touches one of the most important issues in nitrosamines case, the validity of the reference standards which is relative, not only with the difficulties in the purchase but also, and most important, with the presence of ‘‘fake’’ NDSRIs in the compendia lists.

thank you (for one more time :slightly_smiling_face:) dear Yosuke

Christos

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Thank you for sharing. The content and authenticity of reference standards often present significant challenges to researchers. In our research, we have found that the content and authenticity of reference standards supplied by vendors require further confirmation.

Structural characterization of impurities using HR-MS and ¹⁵N two‑dimensional NMR is a prerequisite for the development of robust analytical methods.

The N-nitroso vancomycin independently synthesized by our company has a purity of up to 98%. We already maintain a reference standard collection of more than 150 nitrosamine species and have accumulated extensive experience in the development of NDSRI analytical methods. We look forward to further discussions with you all.

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