Comparison between liquid chromatography–UV detection and liquid chromatography–mass spectrometry for the characterization of impurities and/or degradants present in trimethoprim tablets

The characterization of impurities and/or degradants present in pharmaceutical compounds is an important part of the drug development process. Although LC–UV is commonly employed for impurities and degradant compound determination, LC–MS techniques are proposed in this work to be a viable modern alternative for the characterization of these compounds. LC–UV and LC–MS were compared for the detection of impurities present in different brands of trimethoprim tablets by using an in-line LC–UV–MS system with atmospheric pressure chemical ionization source (APCI) coupled with a reversed-phase gradient HPLC system. It was shown that, although chemical noise was higher when using full-scan LC–MS compared to LC–UV, low level impurities were better detected by mass spectrometry (MS) when modern software algorithms are employed. These included the “Contour” chromatogram algorithm and/or the “component detection algorithm” (CODA). In addition, MS allowed for the simultaneous determination of the molecular masses and some structural information of the impurities and/or degradants. The results also showed a large difference in the purity of trimethoprim among different manufacturers. LC–MS and tandem MS techniques were employed to acquire fragmentation patterns for trimethoprim and its degradants to gain insight into their structures.