Development, evaluation of critical method variables and stability assessment using a Box-Behnken design for the determination of organic impurities in a pharmaceutical dosage form of a centrally acting muscle relaxant drug chlorzoxazone.

Autor: Ettaboina SK; Department of Chemistry, School of Applied Sciences and Humanities (SASH), VIGNAN'S Foundation for Science, Technology & Research (VFSTR), Vadlamudi, India., Nannapaneni S; Department of Chemistry, School of Applied Sciences and Humanities (SASH), VIGNAN'S Foundation for Science, Technology & Research (VFSTR), Vadlamudi, India., Jeedimalla N; Laurus Generics, Inc., Berkeley Heights, New Jersey, USA., Dongala T; Agilent Technologies, Wilmington, Delaware, USA., Muchakayala SK; Analytical Research and Development, Catalent Pharma Solutions, Winchester, Virginia, USA.; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University, Hyderabad, Telangana, India., Katari NK; Department of Chemistry, GITAM School of Science, GITAM Deemed to be University, Hyderabad, Telangana, India.; School of Chemistry & Physics, College of Agriculture, Engineering & Science, Westville Campus, University of KwaZulu-Natal, Durban, South Africa.
Jazyk: angličtina
Zdroj: Biomedical chromatography : BMC [Biomed Chromatogr] 2024 Nov; Vol. 38 (11), pp. e6001. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1002/bmc.6001
Abstrakt: This study validates a stability-indicating LC method for detecting organic impurities in the chlorzoxazone dosage form. Using a Waters X-Select R HSS T3 analytical column, mobile phase of it was made by mixing of water, methanol, and glacial acetic acid in the ratio of 700:300:10 (v/v/v). The drug product and drug substance were subjected to the stress conditions such as acid, base, oxidation, heat, and photolysis as per the recommendations of the International Conference on Harmonization (Q2) methodology. The study revealed the susceptibility of 4-chloro-2-aminophenol to alkaline environments, emphasizing peak homogeneity and stability. The method verification, per ICH guidelines and USP<1225>, established precision, specificity, linearity, accuracy, and robustness for quality control. The mean impurity recovery ranged from 95.5% to 105.2%, the correlation coefficient (r) was greater than 1.000, and the RSD values (n = 6) ranged from 0.6% to 5.1% across the LOQ-150% ranges. Full-factorial design tested final method conditions, evaluating multiple parameters concurrently. Graphical optimization within the design space defined strong method requirements, ensuring consistent and reliable outcomes. The study develops and validates chlorzoxazone stability-indicating methods, employing advanced statistical approaches like design of experiments and factorial design, with resilient conditions established through graphical optimization of the design space.
(© 2024 The Author(s). Biomedical Chromatography published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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