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Volume 20, Issue 8
  • ISSN: 1573-4129
  • E-ISSN: 1875-676X

Abstract

Background

Conventional chromatographic techniques and direct analysis pose challenges in detecting certain potential genotoxic impurities, primarily due to factors such as the absence of a chromophore, low molecular weight, and insufficient chromatographic retention caused by high polarity. One such compound, N, O-Dimethyl Hydroxylamine, is of particular concern due to its structural similarity to Hydroxylamine, a recognized genotoxic impurity.

Methods

In response to this challenge, this article proposes a rapid derivatization approach utilizing Dansyl Chloride, coupled with Liquid Chromatography-Mass Spectrometry (LC-MS) for the detection of the derivatized product in the investigational drug substance. To preserve confidentiality, the specific name and structure of the drug substance have not been disclosed.

Results

The developed method exhibits a reliable range of detection spanning from 5 ppm to 60 ppm with respect to a nominal drug substance concentration of 10 mg/mL. Throughout the method validation process, it demonstrated specificity, sensitivity, linearity, accuracy, and repeatability.

Conclusion

This methodology presents a versatile solution applicable in scenarios where N, O-Dimethyl Hydroxylamine serves as a reagent in the synthesis process of drug substances.

© 2024 Bentham Science Publishers
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2024-09-30
2025-06-18

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/content/journals/cpa/10.2174/0115734129336727240922210156
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Development and Validation of LC-MS Method for Determination of Genotoxic Impurity N, O-Dimethyl Hydroxylamine by Chemical Derivatization in Investigational Drug Substance
Current Pharmaceutical Analysis 20, 800 (2024); https://doi.org/10.2174/0115734129336727240922210156
/content/journals/cpa/10.2174/0115734129336727240922210156
/content/journals/cpa/10.2174/0115734129336727240922210156
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  • Article Type:     Research Article
Keyword(s): chemical derivatization; dansyl chloride; Genotoxic impurity; hydroxylamine; ICH M7; LC-MS

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