ABSTRACT Green analytical chemistry (GAC) aims to achieve faster, safer, accurate, and sustainable analysis by minimizing the hazardous impact of organic solvents on the environment. Here, the focus will be on impurity profiling of pharmaceuticals. This can be done by employing green chromatographic techniques using eco‐friendly solvents, advanced spectroscopic approaches, microextraction, and miniaturization techniques. Pharmaceutical analysis's greenness can be evaluated using various assessment tools and the advanced analytical greenness metric (AGREE). This review comparatively discusses all these tools by highlighting their eco‐friendly nature, methodology, adherence to the 12 major principles of green chemistry, and validation of their results. Furthermore, state‐of‐the‐art case studies utilizing green chemistry principles for impurity profiling of pharmaceuticals have also been discussed, along with their employed techniques and observations, thus offering insights into successful implementation. Still, cost, affordability, scalability, and reproducibility vary across techniques, with, for example, supercritical fluid chromatography (SFC) showing more substantial potential than nuclear magnetic resonance (NMR). Greenness metrics also lack global harmonization, limiting comparability. Challenges like stringent regulatory frameworks and a lack of standardized global policies should be overcome by integrating artificial intelligence (AI) and machine learning (ML), as well as more interdisciplinary collaboration among associated professionals, for the widespread adoption of efficient, sustainable, and eco‐friendlier pharmaceutical analysis techniques. For AI/ML, trustworthiness will require validation and regulatory alignment to ensure they complement rather than replace existing protocols.
Akram et al. (Sat,) studied this question.