• Oliver Scherf-Clavel, Martina Kinzig, Axel Besa, André Schreiber, Clemens Bidmon, Mona Abdel-Tawab, Jonas Wohlfart, Fritz Sörgel, and Ulrike Holzgrabe.
• Institute for Pharmacy and Food Chemistry, Julius-Maximilians University Würzburg, Am Hubland, D-97074, Würzburg, Germany.
• J Pharm Biomed Anal. 2019 Aug 5; 172: 278-284.

AbstractThe recent incidences of contaminated valsartan drug products gave rise to review the suitability of current impurity profiling workflows implemented at authorities and pharmaceutical companies. The major drawback of targeted impurity profiling, where a considerable amount of prior knowledge about possible contaminants is necessary, is the fact that unexpected impurities are overlooked easily. Here, a generic untargeted approach was applied on sartan containing drug products. The untargeted workflow allowed for the discrimination of different batches, different production sites, and differences after changes in the production process. The presented universal workflow makes use of LC-HRMS/MS and multivariate analysis for the interpretation of the data. Sartan samples contaminated with N-nitrosodimethylamine could be very well discriminated from N-nitrosodimethylamine-free samples using the procedure. Furthermore, untargeted approaches revealed two new impurities in various sartans drug products: valeramide and N,N-dimethylvaleramide.Copyright © 2019 Elsevier B.V. All rights reserved.

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