LC-MS and LC-NMR as Complementary Techniques for the Determination of Pharmaceuticals in Dosage Formulations

Pharmaceuticals contain not only pharmacologically active compounds but also a range of excipients. The danger exists that impurities may also be present in such drugs, which may adversely affect their efficacy and even endanger patient health and life. Monitoring the composition of pharmaceutical products is therefore essential. The trace amounts of such impurities in pharmaceuticals are often identified and determined with liquid chromatography coupled with mass spectrometry (LC-MS) or with nuclear magnetic resonance spectroscopy (LC-NMR). With the LC-MS technique, compounds known or suspected to be present in the sample can be identified, but this technique is unsuitable for identifying unknown compounds. In the latter case NMR spectra usually provide reliable structural information; in combination with LC, a mixture of impurities can be identified. The simultaneous use of LC-MS and LC-NMR may supply valuable information on the molecular weight and chemical structure of a compound. This article discusses the merits and shortcomings of both methodologies for determining the structures of unknown compounds. The two approaches should be treated as complementary.