Method Development And Validation Of Lc-Ms/Ms For Analyzing Potential Genotoxic Impurities In Canagliflozin
Keywords:
Genotoxic impurities, LC-MS analysis, canaglifoxin, method development, method validationAbstract
The assessment of toxicological concentrations of possible genotoxic contaminants in drug substances was regarded as an important and challenging discipline . The International Conference and Harmonization (ICH) recommended that most pharmaceutical products be allowed to include 1.5 μg/day of a genotoxic contaminant. The goal study was to develop a quick and accurate method for measuring potential genotoxic impurities (PGIs) in canaglifoxin drug substance. The chromatographic conditions were appropriately optimized with the columns to achieve a decent separation and response of each impurities peak with the canaglifoxin. According to International conference of Harmonization (ICH) criteria for the quantification of each impurity, method validation for LC-MS was carried out regarding specificity, the limit of detection (LOD), the limit of quantification (LOQ), linearity, accuracy (recovery), precision, and solution stability. Correlation observed in the accuracy during method validation hence method can be considered linear and accurate and can be used for testing of genotoxic impurity in canaglifoxin drug substances.
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References
Triplitt C, Cornell S. Canagliflozin treatment in patients with type 2 diabetes mellitus. Clin Med Insights Endocrinol Diabetes 2015; 8: S31526.
Washburn WN. Evolution of sodium glucose co- transporter 2 inhibitors as anti-diabetic agents. Expert Opin Ther Pat 2009; 19:1485-99.
Elder DP, Snodin D, Teasdale A. Analytical approaches for the detection of epoxides and hydroperoxides in active pharmaceutical ingredients, drug products and herbals. J Pharm Biomed Anal 2010; 51:1015-23.
Liu DQ, Kord AS. Analytical challenges in stability testing for genotoxic impurities. TrAC-Trend Anal Chem 2013; 49:108-17.
Genestra M. Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell signal 2007; 19:1807-19.
Ball JC, Young WC, Wallington TJ, Japar SM. Mutagenic properties of a series of alkyl hydroperoxides. Environ Sci Technol.1992; 26:397-9.
Mikhail N. Safety of canagliflozin in patients with type 2 diabetes. Curr Drug Saf 2014; 9: 127-32.
Dietrich E, Powell J, Taylor JR. Canagliflozin: a novel treatment option for type 2 diabetes. Drug Des Dev Ther 2013; 7: 1399.
Swartz, Michael E., and Ira S. Krull. Handbook of analytical validation. CRC Press, 2012.
Chan, Chung Chow, et al., eds. Analytical method validation and instrument performance verification. John Wiley & Sons, 2004.
Ermer, Joachim, and John H. McB Miller, eds. Method validation in pharmaceutical analysis: A guide to best practice. John Wiley & Sons, 2006.
Guideline, ICH Harmonised Tripartite. "Validation of analytical procedures: text and methodology Q2 (R1)." International Conference on Harmonization, Geneva, Switzerland. 2005.
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