Analytical procedures for quality control of pharmaceuticals in terms of residual solvents content: Challenges and recent developments

• DOI: 10.1016/j.trac.2015.09.008
• Publication Date: 2015-12-12T06:53:59Z
• Authors: Maciej Tankiewicz; Jacek Namieśnik; Wiesław Sawicki
• Keywords: Sample Preparation; Pharmacopoeia; Chromatographic Separation; Quality Assessment

Residual solvents play an important role in the synthesis of drugs and in product formulations. In addition, they pose a serious problem, that is toxicity, as many of them exhibit toxic or environmentally hazardous properties. Therefore, constant monitoring of quality control is needed. In this study, we present an overview of regulatory and general methods described by various pharmacopoeias. Then, the most commonly used methodologies for the determination of residual solvents in different pharmaceutical samples are reviewed to demonstrate their limitations, which form the basis of discussion about new methods. Several interesting new alternatives for sample preparation and gas chromatography (GC) separation are presented using examples from recent studies. The techniques described are direct injection, headspace analysis with different modifications and variations, liquid extraction, single-drop microextraction, and solid-phase microextraction. Various GC separation techniques are compared and new solutions to improve sensitivity and efficiency are presented.