title: 'Psychotropics caught in a trap' - adopting a screening approach to specific needs.
abstract: In the field of forensic toxicology, numerous strategies using different types of LC-MS platforms have been developed to set up an ultimate comprehensive screening method. Despite all this research, the question for the detection of a dedicated set of substances arises quite often in daily routine work. In this project, a screening method for the detection of psychotropic drugs based on the open library concept of a recently developed LC-MS(n) screening approach was developed and the effectiveness of a heated ESI-source was evaluated. To set up an individual spectral library all available data of psychotropics from the Toxtyper™ library was transferred to a new library format and complemented by MS, MS(2) and MS(3) data of additional psychotropic compounds. Precursor masses and retention time information of the library were used to trigger data dependent acquisition of MS(n)-spectra. Serum samples were analysed after alkaline liquid-liquid extraction on a Dionex RSLC (Acclaim™ C18 100×2.1C) coupled to a Bruker amaZon speed ion trap. A conventional ESI-source and an ionBooster™ source (IB) were used for ionization. All other LC and MS parameters were adopted from the original screening approach. Identification and result reporting was carried out by a fully automated software script. This screening method finally contains the individual precursor mass and retention time of 105 psychotropic substances and metabolites. Method evaluation was performed using pooled serum samples fortified with 12 different mixtures containing a total of 99 compounds at low therapeutic concentrations (cLOW and 2×cLOW). The customized method (ESI/IB) led to a higher rate of identifications (92%) - especially at low concentration levels (cLOW) - as the comprehensive screening approach (87%). Results from routine analysis with known intake of psychotropic drugs were confirmed with positive findings, if the concentration range was above or around the assumed limit of detection from this evaluation study. The Toxtyper open library concept enables fast and easy generation of new screening methods. The generated screening method is a fast and robust tool for the detection and identification of 105 psychotropics in human serum. Use of the ionBooster source led to a significant increase of the ionization efficiency within this sort of substance class. Evaluation in spiked human serum samples showed detection of low therapeutic levels for the majority of compounds, making the screening applicable for clinical and forensic samples (intoxication and post mortem cases).
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, University Medical Center Freiburg, Germany. Electronic address: juergen.kempf@uniklinik-freiburg.de.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kempf
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, University Medical Center Freiburg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Traber
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, University Medical Center Freiburg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Auwärter
authors.affiliation: Institute of Forensic Medicine, Forensic Toxicology, University Medical Center Freiburg, Germany.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Huppertz
mesh_terms: D057205:Automation, Laboratory; D002853:Chromatography, Liquid; D006358:Hot Temperature; D006801:Humans; D057230:Limit of Detection; D011619:Psychotropic Drugs / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D015813:Substance Abuse Detection / Q000379:methods*
chemical_list: D011619:Psychotropic Drugs
keywords: LC–MS(n) screening; Open library concept; Psychotropic drugs; ionBooster™