Detection and quantification of several synthetic cannabinoids in human plasma by chromatography-mass specrtometry using two new non deuterated internal standards

Synthetic cannabinoids, contained in herbal blends or mixtures commercially available all over the world through shopping-online or in the “smart” shops, are becoming increasingly popular in the last few years [1]. Therefore, their determination in human matrices is an urgent need in forensic toxicology since these substances are abused as an alternative to cannabis products in order to circumvent drug testing [2]. In this work validated methods for the analysis of JWH-018, JWH-073, JWH-122, the 4-methyl derivative of JWH-073, JWH-250, JWH-302 and RCS-8 in human plasma, using GC/MS and LC/MS-MS are presented. After liquid-liquid extraction, the separation of cannabinoids was performed with a gas chromatography system coupled to an ion trap and to a TOF detector. On the other hand liquid chromatography was performed by means of a system equipped with a triple quadrupole mass spectrometer operating in the multiple reaction monitoring mode. The analytical methods were developed using two new non deuterated internal standards specifically synthetized for this purpose. The first, 3-(1-butyl-1H-indol-3-yl)-1-(p-tolyl)-propan-1-one, is endowed with chemical and physical characteristics which make it suitable for the quantitative determination of phenylacetylindoles. The second, 3-(1-butyl-1H-indol-3-yl)-1-(6-methoxy-naphtalen-2-yl)-propan-1-one, is an ideal internal standard for the analysis of naphthoylindoles. The two molecules were designed in a way that they are not controlled drugs on the basis of the Italian law DPR 309/90 (Table I) and therefore they can easily be used in the analytical methods which provide for the simultaneous determination of several synthetic cannabinoids with different structures or when the specific deuterated standard is not available.