Akademik Veri Yönetim Sistemi
Biomedical Chromatography, cilt.40, sa.3, 2026 (SCI-Expanded, Scopus)
Genotoxic impurities (GTIs) in pharmaceutical products represent a critical safety concern because they can induce DNA damage and may lead to mutagenic and carcinogenic effects even at trace concentrations. Consequently, regulatory authorities such as EMA, FDA, and ICH require a risk-based and impurity-specific control strategy, as defined in ICH M7, for active pharmaceutical ingredients (APIs) and finished dosage forms. Due to their structural and physicochemical diversity, GTIs cannot be adequately monitored using a single analytical technique, and method selection must be tailored to the characteristics of each impurity. In this study, impurity-specific analytical methods were developed and validated to demonstrate the practical application of this regulatory approach in different pharmaceutical matrices. GC–MS method was optimized for the determination of volatile alkylating agents, namely methyl, ethyl, and isopropyl methanesulfonate in imatinib mesylate API. LC–MS/MS method was established for the quantification of 5-(4′-(azidomethyl)-[1,1′-biphenyl]-2-yl)-1H-tetrazole, a polar and thermolabile azido impurity in valsartan formulations. Both methods were validated in accordance with ICH Q2(R1) guidelines, demonstrating excellent specificity, linearity (R2 > 0.999), accuracy, and precision, with detection limits sufficient to meet regulatory requirements. Application to commercial products confirmed the robustness of methods and their suitability for routine quality control supporting effective GTI risk management.