Methods used for the detection of toxic components of Callilepis laureola and Senecio latifolius have ranged from the use of thin-layer chromatography, spectrophotometry, and immunoassay to gas chromatography with mass spectrometry. However, each of these techniques has a number of drawbacks. In this chapter, we will describe a solid-phase extraction technique, which allows for the detection and quantitation of the toxins atractyloside and retrorsine in each plant extract using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). This methodology offers high specificity and sensitivity and the ability to identify a broad range of analytes.