Analytical Science and Technology (분석과학)

The Korean Society of Analytical Sciences (한국분석과학회)
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Establishing and validating an HPLC protocol for pralsetinib impurities analysis, coupled with HPLC-MS/MS identification of stress degradation products

  • Rajesh Varma Bhupatiraju (Department of Chemistry, GITAM School of Science, GITAM (Deemed to be University)) ;
  • Pavani Peddi (Department of Chemistry, Prasad V Potluri Siddhartha Institute of Technology) ;
  • Venkata Swamy Tangeti (Department of Chemistry, Tagore Government Arts and Science College (Affiliated to Pondicherry University)) ;
  • Battula Sreenivasa Rao (Department of Chemistry, GITAM School of Science, GITAM (Deemed to be University))
  • Received : 2024.06.06
  • Accepted : 2024.07.30
  • Published : 2024.10.25
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Abstract

This study introduces a novel analytical method for the assessment of pralsetinib impurities and degradation products (DPs), addressing critical gaps in existing methodologies. This research aims to develop a robust HPLC method for impurity analysis, characterize degradation products using LC-MS, and evaluate the environmental impact of the method. The study began by optimizing HPLC conditions with various columns and buffers, ultimately achieving successful separation using an XBridge® RP-C18 column with ethanol as solvent A and 50 mM formic acid at pH 2.9. This setup provided excellent peak resolution and symmetry, essential for reliable stability studies. The developed HPLC method was then adapted for HPLC-MS/MS, enhancing sensitivity and detection efficiency of DPs. Stress degradation studies of pralsetinib under different conditions (acidic, basic, oxidative, thermal, and photolytic) revealed significant degradation under acidic (29.3 %) and basic (21.5 %) conditions, with several DPs identified. Oxidative stress resulted in 19.8 % degradation, while thermal and photolytic conditions caused minimal degradation. HPLC-MS/MS analysis identified structures of five degradation products, providing detailed insights into pralsetinib's stability and degradation pathways. Method validation followed ICH guidelines Q2(R1), confirming method's specificity, selectivity, sensitivity, linearity, accuracy, precision, and robustness. The method exhibited strong linearity with a coefficient of determination (r2) greater than 0.999 for pralsetinib and its impurities. This method advances impurity detection and DPs characterization, ensuring the quality and safety of pralsetinib. Additionally, method's environmental impact was assessed, aligning with sustainable analytical practices. These findings provide essential data on pralsetinib's stability, guiding storage conditions and ensuring its efficacy and safety in pharmaceutical applications.

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References

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