Ines Šahinoviæ (Presenter)
University hospital Osijek
Bio: Ines Šahinoviæ comes from Osijek, Croatia. She has a degree in medical biochemistry and laboratory medicine from Faculty of pharmacy and biochemistry on University of Zagreb, Croatia. Since 2013. she is a resident in medical biochemistry and laboratory medicine in Department of clinical laboratory diagnostics in University hospital Osijek. She works on HPLC and LC-MS/MS technologies. She is a part of a team working in clinical toxicology and therapeutic drug monitoring. Ines is a PhD student in the field of Biomedicine and health on University of Osijek, Croatia. Since 2014. she is young teaching assistant and associate in Department of medical chemistry, biochemistry and clinical chemistry in Faculty of medicine Osijek, University of Osijek.
Authorship: Ines Sahinovic (1,3), Sanja Mandic (1,3), Vesna Horvat (1,3), Dario Mandic (1), Mladen Marcikic (2,3), Vatroslav Seric (1,3)
(1) Department of Clinical Laboratory Diagnostics, University Hospital Osijek, Osijek, Croatia (2) Department of Forensic Medicine, University Hospital Centre Osijek, Osijek, Croatia (3) Faculty of Medicine, Universitiy of Osijek, Osijek, Croatia
| Short Abstract A 34-year-old woman was found dead in her building basement. Drugs and metabolites concentrations in ug/L measured by LCMS/MS in serum were: diazepam 2039, temazepam 148, sertraline 117, N-desmethylsertraline 271, nitrazepam 25, all in or below therapeutic range and nordiazepam 1447, demoxepam 2420, alprazolam 52, mirtazapine 2201 and fluvoxamine 427 above therapeutic range. Although literature shows very low acute toxicity of benzodiazepines and antidepressants, demoxepam and mirtazapine concentrations were above toxic range. Also, combination of these drugs have synergistic pharmacological effects. There is a possibility that multiple drugs overdose caused accidental fall and/or contributed to possible suicide attempt. |
Long Abstract
A 34-year-old woman under psychiatric treatment was found dead in her building basement. Autopsy report stated that cause of death were multiple traumas and injuries sustained after fall from height. There were no obvious information whether she fell or deliberately jumped. Blood and urine samples collected during autopsy were submitted for toxicology analysis.
Drug screening was performed using gass chromatography-mass spectrometry (GCMS-QP 2010 Ultra, Shimadzu) after liquid-liquid extraction using TOXI-TUBE A system (TOXI-LAB, Varian). GCMS drug screening detected presence of anxiolytics alprazolam, diazepam and its active metabolite nordiazepam, hypnotic drug nitrazepam, antidepressants mirtazapine, sertraline and fluvoxamine, analgopyretic metamizole, narcoanalgetic tramadol and coffeine. Drug concentrations in serum were measured by liquid chromatography-tandem mass spectrometry (LCMS/MS-8040, Shimadzu). Quantitation was performed with multiple reaction monitoring (MRM) in positive ionization mode using electrospray ionization interface (ESI). Serum sample was prepared and drugs were quantified using MassTox Series A kit (Chromsystems). Measured concentrations of drugs were: diazepam 2039 ug/L, temazepam 148 ug/L, sertraline 117 ug/L and its metabolite N-desmethylsertraline 271 ug/L in therapeutic range, nitrazepam 25 ug/L below therapeutic range and nordiazepam 1447 ug/L (20-800), demoxepam 2420 ug/L (500-740), alprazolam 53 ug/L (5-50), mirtazapine 2201 ug/L (30-80) and fluvoxamine 427 ug/L (60-230) above therapeutic range.
In forensic and clinical use, immunochemistry analyses are limited with specificity, interferences and analyte range. Qualitative GCMS analysis gives information regarding presence of various analytes, but can’t give information of their concentration, which is of great importance in toxicology. LCMS/MS technology provides complete toxicological picture: qualitative and quantitative information of various analytes and their metabolites. Although literature shows very low acute toxicity of benzodiazepines and antidepressants, demoxepam and mirtazapine concentrations were above toxic range. Also, combination of these drugs have synergistic and additive pharmacological effects causing oversedation, mental confusion and central nervous system depression. There is a possibility that multiple drugs overdose caused accidental fall and contributed to possible suicide attempt.
References & Acknowledgements:
1. Schultz M, Schmoldt A. Therapeutic and toxic blood concentrations of more than 800 drugs and other xenobiotics. Pharmazie 2003;58(7):447-74.
2. Hiemke, et al. AGNP consensus guidelines for therapeutic drug monitoring in psychiatry:Update 2011. Pharmacopsychiatry 2011;44(6):195-235.
| Description | Y/N | Source |
| Grants | no | |
| Salary | no | |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |