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Quantification of Genotoxic Impurities by HPLC in Active Pharmaceutical Ingredient Lorazepam

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Abstract

A simple and selective reversed-phase high performance liquid chromatography method was developed and validated for the quantification of 4-chloroaniline, 2-chloro-N-(4-chloro-2-(2-chlorobenzoyl)phenyl)acetamide and 2-iodo-N-(4-chloro-2-(2-chlorobenzoyl)phenyl)acetamide in lorazepam. 4‑Chloroaniline is used as a raw material and 2-chloro-N-(4-chloro-2-(2-chlorobenzoyl)phenyl)acetamide and 2-iodo-N-(4-chloro-2-(2-chlorobenzoyl)phenyl)acetamide are formed as intermediates in the synthesis of anxiety disorder active pharmaceutical ingredient lorazepam. This method provided excellent sensitivity and a typical target analyte level of 150 ppm. This method was developed on an Agilent poroshell 120 EC-C18 (100 × 4.6 mm, 4 µm) column and a photo diode array detector. The proposed method is specific, linear, accurate and precise. The calibration curve was linear over the concentration range of LOQ to 120% with a correlation coefficient of 0.99. This method has low limits of detection and quantification for all the analytes. Accuracy was observed within the range of 85–115% for all the analytes. The developed method was validated as per the ICH guidelines in terms of specificity, precision, limit of detection, limit of quantification, linearity range and accuracy.

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ACKNOWLEDGMENTS

One of the authors Panga Chinna is highly grateful to the RL Fine Chem Pvt. Ltd., Yelahanka, Bangalore and Tumkur University, Tumkur for the laboratory facility to carry out this work.

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Authors and Affiliations

  1. Department of Studies and Research in Chemistry, Tumkur University, 572103, Tumakuru, Karnataka, India

    Panga Chinna & Shet Prakash M.

  2. RL Fine Chem Pvt Ltd, Yelahanka Industrial Area, Bengaluru, India

    Panga Chinna, Ramesha Andagar Ramakrishna & Yashbir Singh

  3. Department of Chemistry, University College of Science, Tumkur University, 572103, Tumakuru, Karnataka, India

    Swamy Sreenivasa

  4. National Assessment and Accreditation Council, Nagharbhavi, 560072, Bengaluru, Karnataka, India

    Swamy Sreenivasa

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  1. Panga Chinna
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  2. Shet Prakash M.
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Correspondence to Shet Prakash M..

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Chinna, P., Prakash M., S., Ramakrishna, R.A. et al. Quantification of Genotoxic Impurities by HPLC in Active Pharmaceutical Ingredient Lorazepam. J Anal Chem 78, 514–521 (2023). https://doi.org/10.1134/S106193482304007X

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  • DOI: https://doi.org/10.1134/S106193482304007X

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