The cannabis sample is dissolved via a solvent process into a solution. A small portion of this solution is injected into the column. Shortly after injection, the solution evaporates into a gaseous state. This gaseous content then travels through a long capillary column with the help of a carrier gas, usually helium. The column separates the solvent and each individual component, allowing each component to arrive at different times at the end of the column. This time is called the retention time.

After the column separation, the separated components pass through the detector, which could be an electron capture detector or a mass spectrometric detector. These detectors provide proportional responses to the concentrations of the components. In the case of the mass detector, the passing compound is fragmented and charged into pieces. Based on the resulting charge-to-mass ratio, the identity of the compounds can be identified, similarly to a fingerprint.

During the liquid chromatography analysis, the injected solution travels in liquid form, unlike in gas chromatography, where it is vaporized. The carrier solution, typically a light acidic water-based solvent buffer, assists the column in separating the compounds and transporting them to the detector system. The detector is a multiple-mass spectrophotometer, which fragments and charges the compounds multiple times before identifying the charge-to-mass ratio. This method is significantly more selective and sensitive than a simple mass detector system, allowing the determination of each compound at much lower levels.