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Unravelling bioanalytical innovations, degradation processes, and impurity landscapes of VEGFR inhibitors

Pratiksha Misal1, Chaitali Thakare1, Atul Shirkhedkar1

  • 1Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dist-Dhule, MS 425405, India.

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
|July 30, 2026
PubMed

Insights

Analytical methods ensure the quality of VEGFR-targeted tyrosine kinase inhibitors (TKIs). Liquid chromatography-mass spectrometry (LC-MS/MS) offers sensitive quantification for drug monitoring and impurity profiling.

Area of Science:

  • Analytical Chemistry
  • Pharmaceutical Sciences
  • Medicinal Chemistry

Background:

  • Vascular Endothelial Growth Factor Receptor (VEGFR)-targeted small-molecule tyrosine kinase inhibitors (TKIs) are crucial in cancer therapy.
  • Rigorous analytical standards are essential throughout the drug development lifecycle, from pre-formulation to clinical trials.
  • Ensuring the quality, safety, and efficacy of these TKIs necessitates robust analytical methodologies for bioanalysis, stability, and impurity profiling.

Purpose of the Study:

  • To review and highlight chromatographic advances for analyzing VEGFR-targeted TKIs.
  • To discuss the application of various analytical techniques for quality control and regulatory compliance.
  • To provide a framework for future analytical method development for VEGFR-targeted TKIs.

Main Methods:

  • Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) for sensitive quantification (sub ng/mL LLOQs).
  • UPLC-QTOF-MS/MS for structural elucidation of degradants and metabolites during forced degradation studies.
  • High-Performance Thin-Layer Chromatography (HPTLC)/Multiple Layer Chromatography (MLC) for rapid screening, and RP-HPLC/DAD or HPLC-UV for routine quality control.

Main Results:

  • LC-MS/MS and UPLC-MS/MS demonstrate excellent performance with low LLOQs for various VEGFR TKIs (e.g., 0.2 ng/mL for sunitinib, 0.1-0.5 ng/mL for lenvatinib).
  • These methods provide high accuracy (95%-108%) and precision (≤15% RSD) suitable for pharmacokinetics and therapeutic drug monitoring.
  • UPLC-QTOF-MS/MS effectively distinguishes and aids in the structural identification of impurities and metabolites.

Conclusions:

  • LC-MS/MS and High-Resolution Mass Spectrometry (HRMS) offer a robust framework for ensuring VEGFR-TKI quality, safety, and efficacy.
  • Future analytical development should prioritize HRMS-based impurity characterization, AI-driven degradation prediction, green chromatography, and harmonized bioanalytical validation.
  • The review provides essential structural information on TKI degradants and metabolites for regulatory applications and method development.
Keywords:
Analytical method developmentBioanalytical methodsForced degradation studiesImpurity profilingVEGFR TKIs

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