Next-generation liquid chromatography in pharmaceutical quality control: AQbD, ICH Q14/Q2(R2), and green analytics
Year: 2026
Type: article
Abstract: Liquid chromatography (LC) remains a central analytical platform for small-molecule pharmaceutical quality control (QC), supporting specification-based testing of drug substances and products, including assay, impurity profiling, stability, content uniformity, and dissolution testing. This review highlights the transition from conventional to next-generation LC across the broader pharmaceutical analytical lifecycle, distinguishing routine QC from analytical research and development and analytical procedure development. Advanced separation technologies, including core-shell and monolithic columns, ultra-high-performance LC, micro- and nano-LC, and miniaturised platforms, are evaluated in relation to analytical performance, implementation barriers, sustainability, and applicability to routine QC. Their development is conceptually integrated with Analytical Quality by Design (AQbD) and the lifecycle principles of ICH Q14/Q2(R2), encompassing the analytical target profile, critical method attributes and parameters, risk assessment, design of experiments, method operable design region, control strategy, established conditions, knowledge management, validation, and continued verification. Artificial intelligence (AI) and machine learning are examined as complementary tools for retention prediction, chromatographic optimisation, automated experimental design, peak interpretation, robustness assessment, and predictive maintenance, with emphasis on their potential to strengthen AQbD through improved understanding of parameter–performance relationships. However, limitations related to data quality, model explainability, validation, drift, cybersecurity, infrastructure, and regulatory acceptance remain significant. Green analytical strategies are assessed using quantitative and complementary metrics, including AGREE, Analytical Eco-Scale, GAPI, ComplexGAPI, and the Analytical Method Greenness Score. Overall, next-generation LC represents the convergence of advanced separation technologies, lifecycle-oriented regulatory science, digitalisation, and measurable sustainability, while its broader implementation requires robust evidence and practical solutions that balance innovation with analytical reliability, regulatory compliance, cost, and accessibility.
Source: Microchemical Journal
Language: English
Subfield: Analytical Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,000
OpenAlex ID: W7214109138