title: A comprehensive library-based, automated screening procedure for 46 synthetic cannabinoids in serum employing liquid chromatography-quadrupole ion trap mass spectrometry with high-temperature electrospray ionization.
abstract: Considering the vast variety of synthetic cannabinoids and herbal mixtures - commonly known as 'Spice' or 'K2' - on the market and the resulting increase of severe intoxications related to their consumption, there is a need in clinical and forensic toxicology for comprehensive up-to-date screening methods. The focus of this project aimed at developing and implementing an automated screening procedure for the detection of synthetic cannabinoids in serum using a liquid chromatography-ion trap-MS (LC-MS(n)) system and a spectra library-based approach, currently including 46 synthetic cannabinoids and 8 isotope labelled analogues. In the process of method development, a high-temperature ESI source (IonBooster(TM), Bruker Daltonik) and its effects on the ionization efficiency of the investigated synthetic cannabinoids were evaluated and compared to a conventional ESI source. Despite their structural diversity, all investigated synthetic cannabinoids benefitted from high-temperature ionization by showing remarkably higher MS intensities compared to conventional ESI. The employed search algorithm matches retention time, MS and MS(2)/MS(3) spectra. With the utilization of the ionBooster source, limits for the automated detection comparable to cut-off values of routine MRM methods were achieved for the majority of analytes. Even compounds not identified when using a conventional ESI source were detected using the ionBooster-source. LODs in serum range from 0.1 ng/ml to 0.5 ng/ml. The use of parent compounds as analytical targets offers the possibility of instantly adding new emerging compounds to the library and immediately applying the updated method to serum samples, allowing the rapid adaptation of the screening method to ongoing forensic or clinical requirements. The presented approach can also be applied to other specimens, such as oral fluid or hair, and herbal mixtures and was successfully applied to authentic serum samples. Quantitative MRM results of samples with analyte concentrations above the determined LOD were confirmed as positive findings by the presented method.
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology Department, University Medical Center Freiburg, Albertstr. 9, D-79104 Freiburg, Germany.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Huppertz
authors.forename: Stefan
authors.initials: S
authors.lastname: Kneisel
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kempf
mesh_terms: D001331:Automation / Q000379:methods*; D002186:Cannabinoids / Q000097:blood* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006358:Hot Temperature; D006801:Humans; D007211:Indoles / Q000097:blood / Q000737:chemistry; D057230:Limit of Detection; D009281:Naphthalenes / Q000097:blood / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: C586710:(1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone; D002186:Cannabinoids; D007211:Indoles; D009281:Naphthalenes; C587938:(4-methyl-1-naphthyl)-(1-pentylindol-3-yl)methanone
keywords: LC-Msn; automated screening; high-temperature ESI; ion trap; synthetic cannabinoids