Optimization of analytical methods for the determination of pesticide residues in medicinal cannabis according to the European Pharmacopoeia.

The European Pharmacopoeia establishes maximum limits for selected contaminants, including pesticide residues, to ensure the chemical safety of dried herbal drugs and products thereof. The determination of 105 targeted pesticides at concentrations below the maximum residue levels (MRL) requires the employment of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) techniques. The presence of phytocannabinoids and other secondary metabolites in medicinal cannabis poses a particular analytical challenge, as these compounds are co-extracted with the targeted analytes and may substantially affect the analysis. The QuE Verde sorbent demonstrated efficacy in reducing matrix co-extracts, with only methamidophos exhibiting significant losses. The applicability of this method for extract clean-up was successfully demonstrated for both instrumental platforms. The validation study of the LC-MS/MS and GC-MS/MS methods yielded recovery rates ranging from 70% to 120%, with relative standard deviations below 10%. The limits of quantification were achieved within the range of 0.02 to 1.0 mg kg-1 for the LC-amenable analytes and within the range of 0.01 to 0.05 mg kg-1 for the GC-amenable analytes. The validation parameters were found to be in accordance with the requirements specified in the European Commission's guidance document SANTE/11312/2021 v2026. The data demonstrated the suitability of the proposed methods for the determination of all targeted analytes for which the limits of quantification in medicinal cannabis have been established at or below 50% of the MRL.