title: Development and validation of an ultra-fast and sensitive microflow liquid chromatography-tandem mass spectrometry (MFLC-MS/MS) method for quantification of LSD and its metabolites in plasma and application to a controlled LSD administration study in humans.
abstract: Lysergic acid diethylamide (LSD) is a semi-synthetic hallucinogen that has gained popularity as a recreational drug and has been investigated as an adjunct to psychotherapy. Analysis of LSD represents a major challenge in forensic toxicology due to its instability, low drug concentrations, and short detection windows in biological samples. A new, fast, and sensitive microflow liquid chromatography (MFLC) tandem mass spectrometry method for the validated quantification of LSD, iso-LSD, 2-oxo 3-hydroxy-LSD (oxo-HO-LSD), and N-desmethyl-LSD (nor-LSD) was developed in plasma and applied to a controlled pharmacokinetic (PK) study in humans to test whether LSD metabolites would offer for longer detection windows. Five hundred microlitres of plasma were extracted by solid phase extraction. Analysis was performed on a Sciex Eksigent MFLC system coupled to a Sciex 5500 QTrap. The method was validated according to (inter)-national guidelines. MFLC allowed for separation of the mentioned analytes within 3 minutes and limits of quantification of 0.01 ng/mL. Validation criteria were fulfilled for all analytes. PK data could be calculated for LSD, iso-LSD, and oxo-HO-LSD in all participants. Additionally, hydroxy-LSD (HO-LSD) and HO-LSD glucuronide could be qualitatively detected and PK determined in 11 and 8 subjects, respectively. Nor-LSD was only sporadically detected. Elimination half-lives of iso-LSD (median 12 h) and LSD metabolites (median 9, 7.4, 12, and 11 h for oxo-HO-LSD, HO-LSD, HO-LSD-gluc, and nor-LSD, respectively) exceeded those of LSD (median 4.2 h). However, screening for metabolites to increase detection windows in plasma seems not to be constructive due to their very low concentrations. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Steuer
authors.affiliation: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Poetzsch
authors.affiliation: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Lorena
authors.initials: L
authors.lastname: Stock
authors.affiliation: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Lisa
authors.initials: L
authors.lastname: Eisenbeiss
authors.affiliation: Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Schmid
authors.affiliation: Psychopharmacology Research, Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland.
authors.forename: Matthias E
authors.initials: ME
authors.lastname: Liechti
authors.affiliation: Department of Forensic Pharmacology and Toxicology, Zurich Institute of Forensic Medicine, University of Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kraemer
mesh_terms: D002853:Chromatography, Liquid / Q000191:economics / Q000379:methods; D006213:Hallucinogens / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D057230:Limit of Detection; D008238:Lysergic Acid Diethylamide / Q000031:analogs & derivatives / Q000097:blood* / Q000378:metabolism*; D015813:Substance Abuse Detection / Q000191:economics / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000191:economics / Q000379:methods*; D013997:Time Factors
chemical_list: D006213:Hallucinogens; C465027:N-desmethylnorlysergic acid diethylamide; D008238:Lysergic Acid Diethylamide; C118789:2-oxo-3-hydroxylysergic acid diethylamide
keywords: LSD; LSD metabolites; microflow LC-MS/MS; pharmacokinetics