Strategies for the development and optimization of green acetonitrile-free HPLC methods for application in pharmaceutical analysis

In the pharmaceutical industry, high-performance liquid chromatography (HPLC) is of central importance for quality control and the analysis of active pharmaceutical ingredients. Conventional HPLC methods commonly use acetonitrile (ACN) due to its favorable properties, but it’s expensive, toxic, and causes environmental damage, making it necessary to look for safer alternatives. This study presents a systematic approach to developing and optimizing an HPLC pharmaceutical analysis method by replacing ACN and phosphate buffer with methanol and trifluoroacetic acid (TFA). The method was validated for the purity analysis of the radiopharmaceutical PSMA-1007 (¹⁸F) and demonstrates a change towards more environmentally friendly methods in chromatographic analysis. Using multivariate experimental designs, the method was optimized to achieve efficient separation with methanol and TFA. The new method showed comparable performance to conventional methods, is cheaper, and offers environmental benefits such as lower solvent toxicity and lower ecological impact. This work emphasizes the importance of integrating green chemistry principles into method development and provides a guide for applying these practices to various pharmaceutical analyses.