Abstract
Lysergic acid diethylamide (LSD) is a widely used recreational drug. The aim of the present study is to develop a quantitative turboflow LC-MS/MS method that can be used for rapid quantification of LSD and its main metabolite 2-oxo-3-hydroxy LSD (O-H-LSD) in serum and urine in emergency toxicological cases without time-consuming extraction steps. The method was developed on an ion-trap LC-MS/MS instrument coupled to a turbulent-flow extraction system. The validation data showed no significant matrix effects and no ion suppression has been observed in serum and urine. Mean intraday accuracy and precision for LSD were 101 and 6.84 %, in urine samples and 97.40 and 5.89 % in serum, respectively. For O-H-LSD, the respective values were 97.50 and 4.99 % in urine and 107 and 4.70 % in serum. Mean interday accuracy and precision for LSD were 100 and 8.26 % in urine and 101 and 6.56 % in serum, respectively. For O-H-LSD, the respective values were 101 and 8.11 % in urine and 99.8 and 8.35 % in serum, respectively. The lower limit of quantification for LSD was determined to be 0.1 ng/ml. LSD concentrations in serum were expected to be up to 8 ng/ml. 2-Oxo-3-hydroxy LSD concentrations in urine up to 250 ng/ml. The new method was accurate and precise in the range of expected serum and urine concentrations in patients with a suspected LSD intoxication. Until now, the method has been applied in five cases with suspected LSD intoxication where the intake of the drug has been verified four times with LSD concentrations in serum in the range of 1.80–14.70 ng/ml and once with a LSD concentration of 1.25 ng/ml in urine. In serum of two patients, the O-H-LSD concentration was determined to be 0.99 and 0.45 ng/ml. In the urine of a third patient, the O-H-LSD concentration was 9.70 ng/ml.
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References
Passie T, Halpern JH, Stichtenoth DO, Emrich HM, Hintzen A (2008) The pharmacology of lysergic acid diethylamide: a review. CNS Neurosci Ther 14(4):295–314
Gasser P, Holstein D, Michel Y, Doblin R, Yazar-Klosinski B, Passie T, Brenneisen R (2014) Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases. J Nerv Ment Dis 202(7):513–520
Poch GK, Klette KL, Anderson C (2000) The quantitation of 2-oxo-3-hydroxy lysergic acid diethylamide (O-H-LSD) in human urine specimens, a metabolite of LSD: comparative analysis using liquid chromatography-selected ion monitoring mass spectrometry and liquid chromatography-ion trap mass spectrometry. J Anal Toxicol 24(3):170–179
Poch GK, Klette KL, Hallare DA, Manglicmot MG, Czarny RJ, McWhorter LK, Anderson CJ (1999) Detection of metabolites of lysergic acid diethylamide (LSD) in human urine specimens: 2-oxo-3-hydroxy-LSD, a prevalent metabolite of LSD. J Chromatogr B Biomed Sci Appl 724(1):23–33
Chung A, Hudson J, McKay G (2009) Validated ultra-performance liquid chromatography-tandem mass spectrometry method for analyzing LSD, iso-LSD, nor-LSD, and O-H-LSD in blood and urine. J Anal Toxicol 33(5):253–259
Klette KL, Horn CK, Stout PR, Anderson CJ (2002) LC-mS analysis of human urine specimens for 2-oxo-3-hydroxy LSD: method validation for potential interferants and stability study of 2-oxo-3-hydroxy LSD under various storage conditions. J Anal Toxicol 26(4):193–200
Li Z, McNally AJ, Wang H, Salamone SJ (1998) Stability study of LSD under various storage conditions. J Anal Toxicol 22(6):520–525
Berg T, Jorgenrud B, Strand DH (2013) Determination of buprenorphine, fentanyl and LSD in whole blood by UPLC-MS-MS. J Anal Toxicol 37(3):159–165
Canezin J, Cailleux A, Turcant A, Le Bouil A, Harry P, Allain P (2001) Determination of LSD and its metabolites in human biological fluids by high-performance liquid chromatography with electrospray tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 765(1):15–27
Johansen SS, Jensen JL (2005) Liquid chromatography-tandem mass spectrometry determination of LSD, ISO-LSD, and the main metabolite 2-oxo-3-hydroxy-LSD in forensic samples and application in a forensic case. J Chromatogr B Anal Technol Biomed Life Sci 825(1):21–28
Musshoff F, Daldrup T (1997) Gas chromatographic/mass spectrometric determination of lysergic acid diethylamide (LSD) in serum samples. Forensic Sci Int 88(2):133–140
Nelson CC, Foltz RL (1992) Determination of lysergic acid diethylamide (LSD), iso-LSD, and N-demethyl-LSD in body fluids by gas chromatography/tandem mass spectrometry. Anal Chem 64(14):1578–1585
Favretto D, Frison G, Maietti S, Ferrara SD (2007) LC-ESI-MS/MS on an ion trap for the determination of LSD, iso-LSD, nor-LSD and 2-oxo-3-hydroxy-LSD in blood, urine and vitreous humor. Int J Legal Med 121(4):259–265
Caban M, Migowska N, Stepnowski P, Kwiatkowski M, Kumirska J (2012) Matrix effects and recovery calculations in analyses of pharmaceuticals based on the determination of β-blockers and β-agonists in environmental samples. J Chromatogr A 1258:117–127
Dams R, Huestis MA, Lambert WE, Murphy CM (2003) Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: influence of ionization type, sample preparation, and biofluid. J Am Soc Mass Spectrom 14(11):1290–1294
Mueller DM, Duretz B, Espourteille FA, Rentsch KM (2011) Development of a fully automated toxicological LC-MS(n) screening system in urine using online extraction with turbulent flow chromatography. Anal Bioanal Chem 400(1):89–100
Aghajanian GK, Bing OH (1964) Persistence of lysergic acid diethylamide in plasma of human subjects. Clin Pharmacol Ther 5:611–614
Service USDoHaH (2001) Guidance for the industry—bioanalytical method validation
Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal Chem 75(13):3019–3030
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The work was supported by the Swiss Center for Applied Human Toxicology (to M.E.L.).
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Dolder, P.C., Liechti, M.E. & Rentsch, K.M. Development and validation of a rapid turboflow LC-MS/MS method for the quantification of LSD and 2-oxo-3-hydroxy LSD in serum and urine samples of emergency toxicological cases. Anal Bioanal Chem 407, 1577–1584 (2015). https://doi.org/10.1007/s00216-014-8388-1
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DOI: https://doi.org/10.1007/s00216-014-8388-1