Identification of an unknown extraneous contaminant in pharmaceutical product analysis.

摘要

During the content uniformity test of a drug product (tablet formulation), an unknown peak was observed in the HPLC chromatograms. Upon further investigation, it was determined that the unknown peak was originated from an external source and, therefore, the drug product is free of this unknown peak. The next step was to identify the structure of this unknown peak in order to determine the source of this contaminant species. In this paper, we wish to present the strategy and the results of the experiments that led to the identification of this unknown peak. LC-PDA/UV and LC-MS(n) analyses were conducted to obtain the UV spectrum, molecular weight and MS(n) fragmentation pathways of the unknown peak. The MS analysis revealed certain structural features of the unknown species and a number of model compounds that contain such features were then examined for their UV absorbance profiles in an attempt to establish the functional group connectivity within the unknown species. A careful examination of these results in conjunction with the determination of the high-resolution molecular weight led to a short list of potential candidates for the unknown species, among which the most likely one was 1,3-diphenylguanidine. The identification of the unknown contaminant was confirmed by spiking experiments using the authentic compound. The potential source of this contaminant was also identified as derived from the safety filler of the pipette bulb used to prepare the sample solutions during the drug analysis.