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Eco-conscious AQbD-guided stability-indicating RP-UPLC method for analysing Tovorafenib in bulk and dosage forms

Vanga Mohan Goud1, Sarad Pawar Naik Bukke2, Praveen Kumar Kusuma3

  • 1Department of Pharmaceutical Analysis, Joginpally BR Pharmacy College, Telangana, 500075, Hyderabad, India.

Scientific Reports
|December 5, 2025
PubMed

Insights

A new, eco-friendly liquid chromatography method quantifies Tovorafenib, an important drug for pediatric low-grade glioma. This validated method ensures accurate drug analysis for quality control and environmental sustainability.

Area of Science:

  • Analytical Chemistry
  • Pharmaceutical Science
  • Green Chemistry

Background:

  • Tovorafenib, a type II RAF inhibitor, is FDA-approved for pediatric low-grade glioma with specific BRAF alterations.
  • It offers advantages over type I inhibitors due to CNS penetration and lack of paradoxical MAPK activation.

Purpose of the Study:

  • To develop and validate a rapid, robust, and green reversed-phase ultra-performance liquid chromatography (RP-UPLC) method for Tovorafenib quantification.
  • To align method development with ICH Q14 and validation with ICH Q2(R1) guidelines, incorporating Analytical Quality by Design (AQbD) and green analytical chemistry principles.

Main Methods:

  • Utilized a Waters Acquity UPLC BEH C18 column with a specific mobile phase (water:methanol, 62:38 v/v) and PDA detection at 292 nm.
  • Employed ICH Q14 for development and ICH Q2(R1) for validation, including linearity, reproducibility, and forced degradation studies.
  • Assessed environmental impact using various green chemistry metrics (e.g., ComplexMoGAPI, AGREE, RAPI).

Main Results:

  • The method demonstrated excellent linearity (r² = 0.9997) and reproducibility (low %RSD).
  • Tovorafenib showed stability under most forced degradation conditions, with sensitivity to acid hydrolysis.
  • Favorable eco-scores were obtained, indicating a sustainable analytical approach.

Conclusions:

  • The validated RP-UPLC method provides a reliable, sensitive, and sustainable means for Tovorafenib analysis.
  • This approach supports efficient pharmaceutical quality control while adhering to environmental sustainability principles.
  • The study highlights the successful integration of AQbD and green chemistry in analytical method development.
Keywords:
Analytical quality by design (AQbD)Green analytical chemistryRGBfastRP-UPLCTovorafenib

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