ABSTRACT Accurate analysis of pesticide residues in such a complex matrix as cannabis is a challenging task. The aim of this study was to find an optimal way of removing abundant matrix co‐extracts from Quick, Easy, Cheap, Effective, Rugged, and Safe extract prior to its analysis by gas chromatography‐tandem mass spectrometry (GC‐MS/MS). Out of the seven procedures tested, clean‐up with Supel QuE Verde sorbent provided the most satisfactory performance characteristics for 277 targeted pesticides, which is the highest number of these analytes ever investigated within a GC‐MS‐based study focused on cannabis. The criteria set in the SANTE/11312/2021 V2 document were considered to assess the results obtained within the method validation. Recoveries in the range of 70%–120% with repeatability ≤20% were obtained for 219 and 114 pesticides at spiking levels of 0.1 and 0.01 mg/kg, respectively. For a deeper insight into the function of tested sorbents and to understand the effects of interfering matrix co‐extracts, the two‐dimensional GC coupled with the time‐of‐flight MS method was employed for the analysis of all purified extracts. Co‐eluting major phytocannabinoids and free fatty acids were shown to be responsible for high “chemical noise”, increasing limits of quantification of pesticides at respective retention times. Since cannabis chemotypes fairly differ in phytocannabinoid content, the matrix effects, thus performance characteristics, may vary. Under such conditions, validation is recommended for different cannabis chemotypes.

Critical Assessment of Clean‐up Procedures Used for Gas Chromatography‐Mass Spectrometry Analysis of Pesticide Residues in Cannabis Inflorescence