Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method

Panagoula-Stamatina A Ntoupa; Konstantinos P Armaos; Sotiris A Athanaselis; Chara A Spiliopoulou; Ioannis I Papoutsis

doi:10.1016/j.forsciint.2020.110547

Study of the distribution of antidepressant drugs in vitreous humor using a validated GC/MS method

Forensic Sci Int. 2020 Dec:317:110547. doi: 10.1016/j.forsciint.2020.110547. Epub 2020 Oct 17.

Authors

Panagoula-Stamatina A Ntoupa¹, Konstantinos P Armaos¹, Sotiris A Athanaselis¹, Chara A Spiliopoulou¹, Ioannis I Papoutsis²

Affiliations

¹ Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, 75, Mikras Asias street, 11527 Goudi, Athens, Greece.
² Department of Forensic Medicine and Toxicology, School of Medicine, National and Kapodistrian University of Athens, 75, Mikras Asias street, 11527 Goudi, Athens, Greece. Electronic address: ipapoutsis@med.uoa.gr.

PMID: 33129048
DOI: 10.1016/j.forsciint.2020.110547

Abstract

Vitreous humor has become in recent years an important alternative biological fluid in forensic toxicological analysis especially for the investigation of cases where alcohol and drugs of abuse are involved but there is limited scientific information regarding the distribution of antidepressant drugs in this material. This work aimed to study the distribution of antidepressant drugs in vitreous humor and to estimate the blood/vitreous humor concentration ratios of these drugs. For this purpose, a GC/MS method for the simultaneous determination of 9 antidepressant drugs, namely amitriptyline, nortriptyline, citalopram, clomipramine, fluoxetine, maprotiline, mirtazapine, sertraline and venlafaxine, and 4 of their metabolites, namely desmethylmaprotiline, desmethylmirtazapine, desmethylsertraline, O-desmethylvenlafaxine, was developed and validated. The developed method includes solid-phase extraction followed by derivatization with Heptafluorobutyric Anhydride. For all analytes, LOD and LOQ were 1.50 and 5.00ng/mL, respectively, and the calibration curves were linear within the dynamic range of 5.00-500.0ng/mL (R²≥0.990). The absolute recovery was found to be ≥86.3 % for all analytes. The accuracy (%Er) was found to range between -6.58 and 6.18 %, whereas the precision (%RSD) was less than 10.9 % for all analytes. The developed method was successfully applied to vitreous humor samples from 43 blood positive cases for antidepressant drugs. Whenever antidepressant drugs were detected in blood, they were also detected in the respective vitreous humor samples. The vitreous humor/blood concentration ratios were also calculated and were found to range from 0.04-7.07. Citalopram, mirtazapine, and its metabolite desmethylmirtazapine as well as venlafaxine and its metabolite O-desmethylvenlafaxine were the most identified substances in these samples (n≥4) and their results were better statistically evaluated. Our results suggest that vitreous humor could be an appropriate matrix for the determination of antidepressants in postmortem toxicology.

Keywords: Antidepressant drugs; Blood; Distribution; GC/MS; Vitreous humor.

Publication types

Validation Study

MeSH terms

Adult
Aged
Aged, 80 and over
Antidepressive Agents / analysis*
Antidepressive Agents / pharmacokinetics
Female
Forensic Toxicology / methods
Gas Chromatography-Mass Spectrometry
Humans
Limit of Detection
Male
Middle Aged
Solid Phase Extraction
Vitreous Body / chemistry*
Young Adult

Substances

Antidepressive Agents