Assessment of the Greenness of HPLC Methods Employing Common Detectors for Analysis of Caffeine in Pharmaceutical Dosage Forms

Caffeine, the world’s most widespread central nervous system stimulant, naturally exists in various plants species. Caffeine impacts several beneficial physiological functions; accordingly, caffeine is widely consumed from both herbal and pharmaceutical sources. Consequently, caffeine is extracted from different sources and frequently analyzed in pharmaceutical quality control laboratories, necessitating the application of ecofriendly analysis methods. High‐performance liquid chromatography (HPLC) is the most frequently used analytical technique, used for both separation and identification of caffeine in different matrices. Following the green analytical chemistry principles, the presented study evaluates the greenness of 28 HPLC methods using the most commonly used detectors like mass spectrometry, ultraviolet, and diode‐array detectors for caffeine analysis in raw materials and pharmaceutical products. Three commonly used greenness evaluation metric systems were applied, namely, Analytical Greenness Metric (AGREE), National Environmental Method Index (NEMI), and Analytical Ecoscale Evaluation. The method proposed by Shaban et al. was found to be the greenest chromatographic method for caffeine analysis in pharmaceutical dosage forms. It has a fully green circle of NEMI, an AGREE score of 0.86 while in the ESA metric, a score of 90. Additionally, the introduced study discussed the benefits and limitations of greenness evaluation tools, including NEMI, ESA, and AGREE, where it is highly recommended to use more than one tool together in greenness assessments. The results support ecofriendly HPLC assays of caffeine for routine quality control analysis in pharmaceutical companies.