Identification of an unknown extraneous contaminant peak in pharmaceutical product analysis

摘要

By the definition of FDA, drug impurities are components found in a drug product that are neither its drug substances nor excipients. When exceeding certain thresholds, the identification of that unknown impurity is required by regulatory guidelines. The current paper presents a case study for identifying an impurity originating from external contamination by using an approach that combines LC-MS and a systematic way of extracting structural features of the unknown species by examining the UV profiles of a number of structurally relevant model compounds. The unknown contaminant peak was observed at greater than 1percent level during the content uniformity test of a drug product (tablet formulation), and thus needed to be identified. The preliminary investigation strongly indicated that the observed unknown peak was probably an external contaminant and not related to the product. The primary techniques and analytical tools that were used in this study were HPLC with photodiode array UV detector (HPLC-PDA/UV), LC-tandem mass spectrometry (LC-MS/MS) and high resolution mass spectrometry.