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 modem 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.