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Characterization of Elvitegravir and Its Related Impurities Using ESI–LC–MS, NMR Techniques, Method Development and Validation of Its Related Substances by HPLC Method

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Abstract

Elvitegravir (ETV), drug substance, and its eleven process-related impurities have been identified and their structural identification study has been carried out with the aid of 1H, 13C NMR, and ESI–LC–MS spectroscopic techniques. Plausible fragments were also proposed for each impurity to ascertain its structure. Simple, facile, and selective, stability indicating, mass spectrometry compatible HPLC method has been developed and subsequently validated with the validation parameters of specificity, LOD, LOQ, precision at LOQ, linearity, accuracy at LOQ to 120% levels, method precision, intermediate precision studies, and solution stability has also been established. This method encompasses a simple gradient mode of separation with mobile phases—(A) 0.1% trifluoroacetic acid in water and (B) 0.1% trifluoroacetic acid in acetonitrile, the mass sectrometric compatible mobile phase has been chosen for the identification of known, unknown and degradation impurities. To assess the nature of each impurity, whether they are either process-related or degradation-induced, an intensive stress study has also been conducted. From this degradation assessment, all the impurities have been classified as process-related. Further, the assessment of three different manufacturers samples was also executed to show the method applicability and comparison of quality of the different manufacturers drug, and thus this method shall be engaged as a quality inferring tool for the marketed sample.

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Data availability

The datasets generated and analyzed during the current study are available from the corresponding on reasonable request.

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Authors and Affiliations

  1. Department of Chemistry, School of Advance Sciences, Vellore Institute of Technology, Vellore, 632014, India

    Sambandan Elumalai, Sellappan Senthilkumar & Kathavarayan Thenmozhi

  2. Department of Chemistry, National Institute of Technology Warangal, Warangal, Telangana, 506004, India

    Mamidala Srikanth

  3. Department of Chemistry, National Institute of Technology Agartala, Agartala, Tripura, 799046, India

    Venkata Bharat Nishtala

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  1. Sambandan Elumalai
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  2. Sellappan Senthilkumar
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Elumalai performed the experimental work, Sellappan, Mamidala, NIshtala, and Thenmozhi wrote the main manuscript. All authors reviewed the manuscript.

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Correspondence to Venkata Bharat Nishtala or Kathavarayan Thenmozhi.

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Elumalai, S., Senthilkumar, S., Srikanth, M. et al. Characterization of Elvitegravir and Its Related Impurities Using ESI–LC–MS, NMR Techniques, Method Development and Validation of Its Related Substances by HPLC Method. Chromatographia 87, 227–248 (2024). https://doi.org/10.1007/s10337-024-04314-2

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