After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market. Various vendors in online shops claim that HHCP is made from CBD, even though they possess different alkyl chain lengths. An HHCP sample was analyzed by gas chromatography coupled to mass spectrometry (GC‐MS), showing that a mixture of molecules with the same or a similar molecular mass as HHCP was present. Six different substances could be isolated from this sample using column chromatography. Four phenols ((9R)‐HHCP, iso‐HHCP, cis‐HHCP, and abn‐HHCP) and two ketones (possible intermediates to (9R)‐HHCP and abn‐HHCP) were identified by various nuclear magnetic resonance spectroscopy (NMR) techniques. (9S)‐HHCP was obtained in an impure fraction. In addition, a fraction was obtained that showed characteristic molecular and fragment ions consistent with bisalkylated products from the synthesis of similar compounds. The presence of abnormal cannabinoids (abn‐HHCP) and bisalkylated cannabinoids is a confirmation that this sample was produced purely synthetically as initially suspected, as these compounds have not been reported in Cannabis. Chiral derivatization of the phenols with Mosher acid chlorides showed that only iso‐HHCP was present as a scalemic mixture, indicating a good stereocontrol of this synthetic procedure.

Δ⁹-Tetrahydrocannabiphorol (Δ⁹-THCP, THCP) a psychoactive cannabinoid recently found in Cannabis sativa L., is widely used as a legal marijuana substitute. THCP is encountered in sprayed Cannabis, edibles, and vape liquids. The distributors of such products claim that the THCP in use originates from a natural source. The legal status of this substance varies from country to country. THCP and similar cannabinoids with a dibenzoyprane structure have been banned in Switzerland since October 2023. A vape liquid, which contains 90% THCP and 10% terpenes according to the distributor, was analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Besides CBP, CBDP, Δ⁹-THCP and Δ⁸-THCP and some terpenes, other compounds were found which probably result from a synthetic procedure. This sample contained 5-heptylresorcinol, the heptyl homologue of olivetol, a common precursor for the synthesis of tetrahydrocannabinol (THC). Bisalkylated compounds (m/z 476) were found as a result of the reaction of one equivalent of 5-heptylresorcinol with two equivalents of (+)-p-mentha-1,8-dien-4-ol or another precursor. Similar bisalkylated compounds are known as undesired side products of the synthesis of THC. The sample contained unidentified isomers of Δ⁹-THCP, presumably abnormal cannabinoids (abn-Δ⁹-THCP; abn-Δ⁸-THCP) and iso-cannabinoids (iso-THCP). Chiral derivatization with Mosher acid chlorides revealed that the Δ⁹-THCP in the sample was enantiopure.

The vast quantity and high variety of pesticides globally used in agriculture entails considerable risks for the environment and requires ensuring the safety of food products. Therefore, powerful analytical tools are needed to acquire qualitative and quantitative data for monitoring pesticide residues. The development of ambient ionization mass spectrometry methods in the past two decades has demonstrated numerous ways to generate ions under atmospheric conditions and simultaneously to reduce the need for extended sample preparation and circumvent chromatographic separation prior to mass analysis. Swab spray ionization enables the generation of ions directly from swabs via the application of high voltage and solvent flow. In this study, swab sampling of fruit surfaces and subsequent ionization directly from the swab in a modified electrospray ion source was employed for the screening and quantitation of pesticide residues. Aspects regarding sample collection, sampling efficacy on different surfaces, and swab background are discussed. The effect of solvent composition on pesticide-sodium adduct formation and the suppression of ionization by the background matrix have been investigated. Furthermore, a novel approach for the quantitation of pesticide residues based on depletion curve areas is presented. It is demonstrated that swab spray ionization is an effective and quick method for spectral library-based identification and the quantitative analysis of polar contact pesticide residues on food.

The influence of solvent properties on ion generation by swab spray ionization was investigated. The ability of a variety of solvents of different relative permittivity, surface tension, and viscosity to form a stable and reproducible electrospray was examined. It is demonstrated that in swab spray ionization, a crucial balance between solvent composition, applied potential, and the solvent flow fed to the swab head must be maintained. The solvent composition was found to significantly affect the shape of the Taylor cone and the emerging cone jet, which eventually have an impact on the resulting ion yield. The results indicate that the relative permittivity of solvents measured under standard conditions is the main factor governing jet shaping, and consequently, the ionization efficacy. Short jets, which are required for maximum ion yield, were observed for solvents with relative permittivity ε_r higher than 25. Solvents exhibiting lower relative permittivity required the addition of 20% to 60% methanol to limit the jet length and to avoid the ineffective dripping pulsation. The observed effects were compared to conventional electrospray ionization and paper spray ionization.

Bent metallocene dichlorides (Cp₂MCl₂, M = Ti, Mo, Nb, …) have found interest as anti-cancer drugs in order to overcome the drawbacks associated with platinum-based therapeutics. However, they suffer from poor hydrolytic stability at physiological pH. A promising approach to improve their hydrolytic stability is the formation of host-guest complexes with macrocyclic structures, such as cyclodextrins. In this work, we utilized nanoelectrospray ionization tandem mass spectrometry to probe the interaction of titanocene dichloride with β-cyclodextrin. Unlike the non-covalent binding of phenylalanine and oxaliplatin to β-cyclodextrin, the mixture of titanocene and β-cyclodextrin led to signals assigned as [βCD + Cp₂Ti–H]⁺, indicating a covalent character of the interaction. This finding is supported by titanated cyclodextrin fragment ions occurring from collisional activation. Employing di- and trimethylated β-cyclodextrins as hosts enabled the elucidation of the influence of the cyclodextrin hydroxy groups on the interaction with guest structures. Masking of the hydroxy groups was found to impair the covalent interaction and enabling the encapsulation of the guest structure within the hydrophobic cavity of the cyclodextrin. Findings are further supported by breakdown curves obtained by gas-phase dissociation of the various complexes.

Hexahydrocannabiphorol (HHCP) is an emerging semisynthetic cannabinoid, which has been known since 1942 from research of tetrahydrocannabinol (THC) analogs and homologs. After the ban of hexahydrocannabinol (HHC) in many European Countries HHCP emerged as a replacement among other similar compounds. First countries already placed HHCP under their narcotic substance law. The aim of this research was to identify human Phase I and II metabolites in urine after oral HHCP consumption. Enzymatic immunoassays of urine samples were tested negative for cannabinoids after a single oral consumption of 4‐mg HHCP from a Δ⁹‐THC abstinent volunteer. The HHCP sample consumed in the self‐experiment was purchased from an online store and analyzed beforehand using GC–MS. LC–HR‐MS/MS and GC–MS after derivatization were used for the identification of metabolites. Hydroxylated metabolites were found with hydroxylation on the side chain or on the alicyclic part of the molecule. Bishydroxylated HHCP metabolites were found in similar abundance as the monohydroxy metabolites. All of the bishydroxylated metabolites besides a minor metabolite had a hydroxyl group on the side chain and another hydroxyl group on the alicyclic part of the molecule. In addition, the corresponding glucuronides were identified by LC–HR‐MS/MS. The exact positions and stereochemistry of the hydroxylation sites could not be determined. Due to the extensive metabolism of HHCP and the lacking cross‐reactivity of urine samples after consumption in Δ⁹‐THC specific immunoassays, it is recommended to include HHCP metabolites in routine screening methods. Monohydroxylated and bishydroxylated metabolites of HHCP and their respective glucuronides are suggested as forensic targets.