QbD-guided HPTLC method development and validation for quantitative estimation of anticancer drugs

Abstract

Background: Olaparib, Abiraterone acetate, and Pazopanib are critical anticancer agents used in the treatment of breast/ovarian, prostate, and renal cancers, respectively. Ensuring their quality through precise, cost-effective analytical techniques is vital for routine quality control (QC). Given their clinical importance, a robust method capable of quantifying these drugs individually and indicating their stability under stress is highly desirable. Methodology: High-performance thin-layer chromatography (HPTLC) methods were developed for each drug, guided by a Quality by Design (QbD) approach. A 2³ factorial design was employed to optimize three critical method parameters: mobile phase composition, chamber saturation time, and detection wavelength. Chromatographic analysis was performed on aluminum-backed silica gel plates with detection wavelengths set at 278 nm (Olaparib), 255 nm (Abiraterone acetate), and 254 nm (Pazopanib). Method validation followed ICH Q2(R2) guidelines, assessing linearity, accuracy, precision, LOD/LOQ, specificity, and robustness. Forced degradation under acidic, basic, oxidative, thermal, and photolytic conditions was evaluated to assess the stability-indicating capability. Results and Discussion: All methods exhibited strong linearity (r² > 0.997), high accuracy (98–102% recovery), and precision (%RSD < 2). Sensitivity was excellent, with LOD as low as 28 ng/spot for Olaparib. Under stress, degradation ranged from 5% to 20%, with distinct degradant peaks and peak purity indices of> 0.995, confirming no co-elution and indicating stability. The validated methods were successfully applied to stressed marketed formulations. Conclusion: The QbD-optimized HPTLC methods are accurate, economical, and stability-indicating, making them suitable for routine QC of Olaparib, Abiraterone acetate, and Pazopanib in pharmaceutical dosage forms.