What good is a mass spectrometer if you have an NMR?

As a result of improvements in mass spectrometry ionization techniques (MALDI and electrospray) and advances in mass analyzer technology (orbitraps and q-ToFs), it is now possible to obtain accurate mass measurements (Fig.1) of natural products even in very complex biological matrices. Nonetheless, the most common application of mass spectrometry in natural products research is for a final confirmation of molecular formula on compounds already purified and characterized with NMR. NMR has significant advantages over mass spectrometry of enabling molecular connectivity to be established, and providing data that is far less dependent on instrument parameters. Thus, it is no surprise that NMR is the technique of choice for structure elucidation of unknowns, and it will likely continue to be so for the foreseeable future. However, mass spectrometry has complementary capabilities that can be a major boon to natural products researchers. For example, it is possible using mass spectrometry to track compounds throughout the isolation process, thereby correlating their presence with biological activity (Fig.2). This approach helps to overcome some of the biases that are inherent in the isolation process, and facilitates dereplication and the identification of analogs and synergists. Another important application of mass spectrometry in natural products research is its use for studying bioactivity and mechanism of action. This can be accomplished using targeted or untargeted metabolomics, or proteomics. This talk will include an exploration of some of the major strengths and limitations of mass spectrometry as a tool for natural products research, highlighting how recent advances in instrumentation have enabled new applications, and identifying areas with the greatest potential for future development.

Fig. 1: Orbitrap mass analyzer superimposed on an orbitrap mass spectrum of the alkaloid berberine. Mass accuracy of 2 ppm was obtained without internal calibration.

Fig. 2: Correlation of constituent profiles with bioactivity of fractions from a Hydrastis canadensis extract. The presence of flavonoids in fraction 4 correlates with its superior antimicrobial activity (low MIC).