ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Degradation products of proguanil — 4-chloroaniline and related components with regard to genotoxicity

Katharina Schulz, Ulrich Oberdieck, and Werner Weitschies

Analytical Development, Bayer Healthcare Pharmaceuticals, Müllerstrasse 178, 13353, Berlin, Germany

E-mail: katharina.schulz4@gmx.de

Abstract: In the event of genotoxic impurities in drug products, knowledge of the origin and fate of these components is of particular importance. In the present study, commercially available proguanil tablets (Paludrine®) were investigated in respect of formation of the main degradation product, 4-chloroaniline (PCA), which is known to be genotoxic. The investigations made use of high performance liquid chromatography coupled with fluorescence detection (HPLC-FLD) and gas chromatography coupled with flame ionisation detection (GC-FID) systems. In addition, proposals for the structure of further proguanil degradation products were developed based on results obtained by mass spectroscopy (HPLC-MS). Database analysis using DEREK, MCASE, and Vitic was performed to obtain an initial toxicological evaluation of the proposed chemical structures. Finally, the absence of the newly established structures in stored proguanil tablets was verified.

Keywords: genotoxicity – 4-chloroaniline – proguanil – degradation products

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-013-0333-9

Chemical Papers 67 (6) 657–666 (2013)