HPLC and LC/MS Analysis of Pharmaceutical Container Closure System Leachables and Extractables

The term leachables refers to impurities in pharmaceutical products whose origin is the pharmaceutical container closure system in either direct or indirect contact with the formulation. Potential leachables identified through laboratory studies of pharmaceutical container closure system components are referred to as extractables. Extractables and leachables are most often chemical additives to plastic and elastomeric container closure system components, or organic residues on metal and glass surfaces. HPLC and LC/MS are used for the detection, identification and quantitation of extractables and leachables. This review presents and discusses the extractables/leachables issue within the contexts of both regulatory and analytical sciences. It also thoroughly reviews and describes the recent applications of both HPLC and LC/MS to this challenging and intriguing issue in pharmaceutical development.