Analysis of impurities in pharmaceuticals by LC‐MS with cold electron ionization

Abstract

Pharmaceuticals require careful and precise determination of their impurities that might harm the user upon consumption. Although today, the most common technique for impurities identification is liquid chromatography-mass spectrometry (LC-MS/MS), it has several downsides due to the nature of the ionization method. Also, the analyses in many cases are targeted thus despite being present, some of the compounds will not be revealed. In this paper, we propose and show a new method for untargeted analysis and identification of impurities in active pharmaceutical ingredients (APIs). The instrument used for these analyses is a novel electron ionization (EI) LC-MS with supersonic molecular beams (SMB). The EI-LC-MS-SMB was implemented for analyses of several drug samples spiked with an impurity. The instrument provides EI mass spectra with enhanced molecular ions, named Cold EI, which increases the identification probabilities when the compound is identified with the aid of an EI library like National Institute of Standards and Technology (NIST). We analyzed ibuprofen and its impurities, and both the API and the expected impurity were identified with names and structures by the NIST library. Moreover, other unexpected impurities were found and identified proving the ability of the EI-LC-MS-SMB system for truly untargeted analysis. The results show a broad dynamic range of four orders of magnitude at the same run with a signal-to-noise ratio of over 10 000 for the API and almost uniform response.

Comprehensive Controller for Super Sonic Molecular Beam Gas Chromatograph Mass Spectrometer

“…GC-MS with Cold EI improves all the central performance aspects of GC-MS and uniquely provides enhanced molecular ions, improved sample identification, significantly extended range of compounds amenable for analysis, uniform response to all analytes (internal quantitation), faster analysis, greater selectivity, and lower limits of detection [25][26][27][28][29][30][31][32][33].…”

“…The molecular ion is the most (and many times the only) characteristic ion as the fragmentation pattern can be similar for many compounds, and therefore it is often vital for sample compound identification. GC-MS with Cold EI improves all the central performance aspects of GC-MS and uniquely provides enhanced molecular ions, improved sample identification, significantly extended range of compounds amenable for analysis, uniform response to all analytes (internal quantitation), faster analysis, greater selectivity, and lower limits of detection [25][26][27][28][29][30][31][32][33].…”