Unexpected formation of dichloroacetic and trichloroacetic artefacts in gas chromatograph injector during Cannabidiol analysis

Abstract

The knowledge about the stability of compounds and possible ways of their transformation in the process of sample preparation for analysis and during analysis itself is very helpful in the assessment of possible errors which can appear when an accurate and precise estimation of compound concentration in tested samples is attempted. The present paper shows that a significant amount of CBD present in the blood/plasma sample analyzed by means of GC transforms in the hot GC injector not only to 9α-hydroxyhexahydrocannabinol, 8-hydroxy-iso-hexahydrocannabinol, Δ9-tetrahydrocannabinol, Δ8-tetrahydrocannabinol, and cannabinol but also to the trichloroacetic esters of Δ9-THC and Δ8-THC and, unexpectedly, to their dichloroacetic esters when trichloroacetic acid is used as protein precipitation agent. The increase of GC injector temperature favors the formation of dichloroacetic esters of Δ9-THC and Δ8-THC in relation to their trichloroacetic ones. The appearance of dichloroacetic esters of Δ9-THC and Δ8-THC among CBD transformation products is probably the result of the thermal decomposition of their trichloroacetic esters. The transformation of trichloroacetic derivatives of organic compounds into their dichloroacetic derivatives in GC injector has not been reported yet. The instability of trichloroacetic derivatives of Δ8-/Δ9-THC during their GC analysis is probably accounts for the lack of their GC-MS spectra in the databases. NMR, GC-MS and LC-MS spectra of the newly discovered derivatives constitute an important element of the work. The obtained results demonstrate why the use of trichloroacetic acid for plasma samples deproteinization should be avoided when CBD and/or THC are determined by GC.

Keywords: CBD transformation; Dichloroacetic esters of THC; GC–MS; Plasma precipitation; Trichloroacetic esters of THC.