Electron impact-induced fragmentation of the trimethylsilyl derivatives of monohydroxy-hexahydrocannabinols

Abstract

Monohydroxylated derivatives of hexahydrocannabinols were synthesized by catalytic hydrogenation of hydroxytetrahydrocannabinols over a rhodium/alumina catalyst, reduction of tetrahydrocannabinol epoxides with lithium aluminium hydride, or by reaction of tetrahydrocannabinols with hydrogen peroxide. The electron impact-induced fragmentation of their trimethylsilyl ethers was investigated with the aid of deuterium labelling. Most of the compounds gave characteristically different mass spectra with abundant, diagnostically useful fragment ions. As hexahydrocannabinols containing hydroxy groups in all metabolically sensitive positions were readily prepared by the above methods, these provided reference samples for identification of new hydroxylated metabolites of isomeric tetrahydrocannabinols following hydrogenation. The method was validated by application to metabolites of delta-9(11)-tetrahydrocannabinol.

Mass Spectrometric Fragmentation of Trimethylsilyl and Related Alkylsilyl Derivatives

“…Bis‐ TMS derivatives of compounds containing catechol groups frequently eliminate the elements of tetramethylsilane to give cyclic products. Examples are the fragment ions from o‐dihydroxybenzenes (Horvat & Senter, ), 9,10‐phenanthrenequinone ( aw ) (Toriba et al, ), 2‐hydroxyhexahydrocannabinol ( ax ) (Harvey & Brown, ), gingerols (see below) (Harvey, ) and flavonoids (e.g. ay ) (Creaser et al, ; Kim et al, , Sakushima & Nishibe, ).…”

“…Two papers (Harvey, ; Harvey & Brown, ) report several TMS‐induced fragmentations of hydroxy‐hexahydrocannabinols (hydroxy‐HHC) allowing the positions of hydroxylation to be determined. Loss of TMS‐OH again dominated the spectrum of the bis ‐TMS derivative of 8α‐HHC ( 195 ) for the same stereochemical reason as in the Δ 8 ‐THC isomer but in this case a subsequent loss of the C11‐methyl radical produced the base peak at m/z 371 ( kw , Scheme , Fig.…”

“…EI spectra of the TMS derivatives of (a) 8α‐hydroxy‐HHC ( 195 ), (b) 8β‐hydroxy‐HHC ( 196 ), (c) 7α‐hydroxy‐HHC ( 197 ) and (d) 7β‐hydroxy‐HHC ( 198 ). (Adapted from Harvey and Brown ()).…”

“…Proposed mechanism for the formation of the fragment ion at m/z 461 ( kz ) from the TMS derivative of 10‐hydroxy‐HHC ( 199 ) (Harvey & Brown, ).…”

“…a) is totally dominated by the [M − 15] + ion at m/z 461 ( kz ). Deuterium labeling indicates loss of a non‐TMS methyl radical and the mechanism in Scheme has been proposed (Harvey & Brown, ).…”