Abstract
A gas chromatographic–mass spectrometric (GC–MS) method in positive ion chemical ionization mode in combination with a solid phase extraction was optimized for new-generation antidepressants and their metabolites in postmortem blood, brain tissue, and hair. Twelve antidepressants and their active metabolites (i.e., mirtazapine, viloxazine, venlafaxine, citalopram, mianserin, reboxetine, fluoxetine, fluvoxamine, sertraline, maprotiline, melitracen, paroxetine, desmethylfluoxetine, desmethylmianserin, desmethylmirtazapine, desmethylsertraline, desmethylmaprotiline, desmethylcitalopram, and didesmethylcitalopram) could be quantified. In this article, in addition to the validation of the GC–MS method, four postmortem cases are discussed to demonstrate the usefulness of the described method in forensic toxicology. In these cases, sertraline, fluoxetine, citalopram, and trazodone in combination with their active metabolites were quantified. Blood concentrations ranged from subtherapeutic to toxic concentrations, while brain to plasma ratios ranged from 0.8 to 17. Hair concentrations ranged from 0.4 to 2.5 ng/mg depending on the compound and hair segment.
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Kincaid RL, McMullin MM, Crookham SB, Rieders F (1990) Report of a fluoxetine fatality. J Anal Toxicol 14:327–329
Wenzel S, Aderjan R, Mattern R, Pedal I, Skopp G (2006) Tissue distribution of mirtazapine and desmethylmirtazapine in a case of mirtazapine poisoning. Forensic Sci Int 156:229–236
Goeringer KE, Raymon L, Christian GD, Logan BK (2000) Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases. J Forensic Sci 45:633–648
Keller T, Zollinger U (1997) Gas chromatographic examination of postmortem specimens after maprotiline intoxication. Forensic Sci Int 88:117–123
Luchini D, Morabito G, Centini F (2005) Case report of a fatal intoxication by citalopram. Am J Forensic Med Pathol 26:352–354
de Meester A, Carbutti G, Gabriel L, Jacques JM (2001) Fatal overdose with trazodone: case report and literature review. Acta Clin Belg 56:258–261
Azaz-Livshits T, Hershko A, Ben-Chetrit E (2002) Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature. Pharmacopsychiatry 35:112–115
Goeringer KE, McIntyre IM, Drummer OH (2001) Postmortem tissue concentrations of venlafaxine. Forensic Sci Int 121:70–75
Kelly CA, Dhaum N, Laing WJ, Strachan FE, Good AM, Bateman DN (2004) Comparative toxicity of citalopram and the newer antidepressants after overdose. J Toxicol Clin Toxicol 42:67–71
Drasch G, Dahlmann F, von Meyer L, Roider G, Eisenmenger W (2008) Frequency of different anti-depressants associated with suicides and drug deaths. Int J Legal Med 122:115–122
Koski A, Vuori E, Ojanpera I (2005) Newer antidepressants: evaluation of fatal toxicity index and interaction with alcohol based on Finnish postmortem data. Int J Legal Med 119:344–348
Adson DE, Erickson-Birkedahl S, Kotlyar M (2001) An unusual presentation of sertraline and trazodone overdose. Ann Pharmacother 35:1375–1377
Rogde S, Hilberg T, Teige B (1999) Fatal combined intoxication with new antidepressants. Human cases and an experimental study of postmortem moclobemide redistribution. Forensic Sci Int 100:109–116
Singer PP, Jones GR (1997) An uncommon fatality due to moclobemide and paroxetine. J Anal Toxicol 21:518–520
McIntyre IM, King VK, Staikos V, Gall J, Drummer OH (1997) A fatality involving moclobemide, sertraline, and pimozide. J Forensic Sci 42:951–953
Dams R, Benijts THP, Lambert WE, Van Bocxlaer JF, Van Varenbergh D, Peteghem CV, De Leenheer AP (2001) A fatal case of serotonin syndrome after combined moclobemide–citalopram intoxication. J Anal Toxicol 25:147–151
Stimpfl T, Reichel S (2007) Distribution of drugs of abuse with specific regions of the human brain. Forensic Sci Int 170:179–182
Musshoff F, Madea B (2007) Analytical pitfalls in hair testing. Anal Bioanal Chem 388:1475–1494
Pragst F, Balikova M (2006) State of the art in hair analysis for detection of drug and alcohol abuse. Clin Chim Acta 370:17–49
Kintz P, Tracqui A, Mangin P (1992) Detection of drugs in human hair for clinical and forensic application. Int J Legal Med 105:1–4
Wille S, Cooreman S, Neels H, Lambert W (2008) Relevant issues in the monitoring and the toxicology of antidepressants. Crit Rev Clin Lab Sci 45:25–89
Wille SMR, Van hee P, Neels HM, Van Peteghem CH, Lambert WE (2007) Comparison of electron and chemical ionization modes by validation of a gas chromatographic–mass spectrometric assay of new generation antidepressants and their active metabolites in plasma. J Chromatogr A 1176:236–245
Maurer HH, Pfleger K, Weber AA (2007) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites, 3rd edn. Wiley-VCH, Weinheim
Maurer HH, Kraemer T, Kratzsch C, Peters FT, Weber AA (2002) Negative ion chemical ionization gas chromatography–mass spectrometry and atmospheric pressure chemical ionization liquid chromatography–mass spectrometry of low-dosed and/or polar drugs in plasma. Ther Drug Monit 24:117–124
Couper FJ, McIntyre IM, Drummer OH (1995) Extraction of psychotropic drugs from human scalp hair. J Forensic Sci 40:83–86
Couper FJ, McIntyre IM, Drummer OH (1995) Detection of antidepressant and antipsychotic-drugs in postmortem human scalp hair. J Forensic Sci 40:87–90
Smyth WF, Leslie JC, McClean S et al (2006) The characterisation of selected antidepressant drugs using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry. Rapid Commun Mass Spectrom 20:1637–1642
Müller C, Vogt S, Goerke R, Kordon A, Weinmann W (2000) Identification of selected psychopharmaceuticals and their metabolites in hair by LC/ESI-CID/MS and LC/MS/MS. Forensic Sci Int 113:415–421
Wille SMR, Maudens KE, Van Peteghem CH, Lambert WE (2005) Development of a solid phase extraction for 13 ‘new’ generation antidepressants and their active metabolites for gas chromatographic-mass spectrometric analysis. J Chromatogr A 1098:19–29
US Department of Health and Human Services Food and Drug Administration-Center for Drug Evaluation and Research (CDER) (2001) Guidance for industry, bioanalytical method validation. Rockville, IN
Fisar Z, Fuksova K, Sikora J, Kalisova L, Velenovska M, Novotna M (2006) Distribution of antidepressants between plasma and red blood cells. Neuroendocrinol Lett 27:307–313
Hinderling PH (1997) Red blood cells: a neglected compartment in pharmacokinetics and pharmacodynamics. Pharmacol Rev 49:279–295
Bolo NR, Hode Y, Nedelec JF, Laine E, Wagner G, Macher JP (2000) Brain pharmacokinetics and tissue distribution in vivo of fluvoxamine and fluoxetine by fluorine magnetic resonance spectroscopy. Neuropsychopharmacology 23:428–438
Moffat AC, Osselton MD, Widdop B (2004) Clarke’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material. Pharmaceutical Press, London
Renshaw PF, Guimaraes AR, Fava M et al (1992) Accumulation of fluoxetine and norfluoxetine in human brain during therapeutic administration. Am J Psychiatry 148:1592–1594
Martin A, Pounder DJ (1992) Postmortem toxicokinetics of trazodone. Forensic Sci Int 56:201–207
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Wille, S.M.R., De Letter, E.A., Piette, M.H.A. et al. Determination of antidepressants in human postmortem blood, brain tissue, and hair using gas chromatography–mass spectrometry. Int J Legal Med 123, 451–458 (2009). https://doi.org/10.1007/s00414-008-0287-6
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DOI: https://doi.org/10.1007/s00414-008-0287-6