Abstract: A sample may be prepared and then analyzed using a liquid chromatography with tandem mass spectrometry system to determine presence and concentration of herbicide(s) present in the sample. In some examples, the method involves providing a sample containing one or more herbicides and adding a base to the sample. The base may increase the pH of the sample to ?12, thereby hydrolyzing esters of the one or more herbicides. The method may further involve, subsequent to hydrolyzing the esters of the one or more herbicides, adding an acid to the sample so as to lower the pH of the sample to ?3. Once prepared, the sample can be injected into a liquid chromatography instrument to separate the herbicide molecules from other molecules present in the sample before being ionized and characterized by mass-to-charge ratio and relative abundance using one or more mass spectrometers.