Drug compounds undergo a range of biotransformations in the body before they are excreted. The nature and kinetics of each of the metabolic steps are important characteristics of a drug candidate, determining its clearance rates and potential toxicity. It is therefore crucial to understand the metabolic transformations of a drug already at an early stage in the development process. Over the last decades, approaches based on liquid chromatography-mass spectrometry (LC-MS) have become the method of choice for metabolic profiling in in vitro and in vivo drug metabolism experiments, mainly due to their high sensitivity. However, the structural elucidation of the MS-detected metabolites remains challenging, as there are usually multiple isomers to consider. The type of metabolic reaction is often straightforward to infer from the mass difference between the metabolite and the drug molecule; for instance, hydroxylation corresponds to +16 u. However, determining the exact transformation site in the drug molecule is more challenging, as regioisomers tend to have very similar MS/MS fragmentation patterns that are also difficult to predict without reference standards. Final elucidation of metabolite structures often relies on time-consuming isolation of the metabolite from the sample matrix, followed by NMR analysis, and/or comparison to synthetic reference standards, which are usually not commercially available.