Liquid chromatography (LC) can be used to isolate compounds of interest from mixtures for further analysis, using techniques such as mass spectrometry and nuclear magnetic resonance (NMR). The conditions of such isolation methods can lead to degradation of the isolated compounds of interest, which is obviously a major problem if a goal of the isolation is to identify the compound of interest. In this installment of “LC Troubleshooting,” we discuss strategies that can be used to minimize the likelihood of compound degradation in the isolation process.