INTRODUCTION

The term ‘‘leachables’’ refers to impurities in pharmaceutical products with an origin of the pharmaceutical container closure system in either direct or indirect contact with the formulation [1]. Pharmaceutical regulatory authorities, such as European Medicinal Agency (EMA) and Food and Drug Administration (FDA), periodically issue guidelines on leachables quantitation in pharmaceutical manufacturing and finished drug product. These guidelines make it critical to be able to develop an accurate and generalized method at ultra-low levels for the leachable impurities. High-performance liquid chromatography-mass spectrometry (LC/MS) has had a significant impact on drug development over the past decade because LC/MS meets many of the demands of drug development, such as sensitivity, selectivity, speed, and cost effectiveness [2]. The combination of HPLC with mass spectrometry allows LC/MS to accomplish structural analysis (i.e., molecular structure elucidation), qualitative analysis (i.e., high sensitivity confirmation of the presence or absence of a target analyte), and high sensitivity quantitative analysis for leachables impurity analysis [3]. However, there are still specific challenges to be addressed for the leachables impurity method development using LC/MS. This white paper provides a summary of the best strategies for method development of leachables analysis at BA Sciences Inc (BA). Read More >