Main Article Content
Abstract
Impurity profiling is a critical aspect of pharmaceutical quality
control, as even trace-level contaminants can impact drug safety, efficacy, and
regulatory compliance. The stringent requirements of ICH guidelines (Q3A
Q3D, M7, Q3D) have driven the development of advanced analytical methods
capable of detecting, quantifying, and structurally characterizing impurities at
sub-ppb levels. Recent technological advancements including high-resolution
mass spectrometry (HRMS), multidimensional chromatography (2D-LC), and
hyphenated techniques such as LC–MS/NMR and LC–IMS–MS have
substantially improved sensitivity, selectivity, and structural elucidation
capabilities. Complementary innovations in ambient ionization methods
(DESI, DART, paper spray), process analytical technology (PAT) sensors, and
chemometric and AI-based data analytics now allow high-throughput impurity
screening, real-time process monitoring, and predictive profiling. These
integrated approaches facilitate risk-based impurity management, rapid
detection of genotoxic and trace-level impurities, and enhanced compliance
with regulatory expectations. Furthermore, the development of universal
spectral libraries, standardized data frameworks, and automated analytical
workflows promises to streamline method development, cross-laboratory
reproducibility, and regulatory submissions. This review summarizes the
recent trends in pharmaceutical impurity analysis, highlighting the
convergence of advanced instrumentation, data-driven modeling, and
regulatory-aligned strategies, and emphasizes how these innovations are
transforming impurity detection, characterization, and control. The adoption
of such integrated approaches is expected to improve patient safety, optimize
manufacturing efficiency, and enable predictive quality assurance, positioning
impurity profiling as a cornerstone of modern pharmaceutical development.