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 (R≥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.
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http://dx.doi.org/10.1016/j.forsciint.2020.110547 | DOI Listing |
Sci Rep
January 2025
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.
The orbitofrontal cortex (OFC) is a large cortical structure, expansive across anterior-posterior axes. It is essential for flexibly updating learned behaviors, and paradoxically, also implicated in inflexible and compulsive-like behaviors. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences.
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January 2025
Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, and School of Medicine, Tzu Chi University, Hualien, Taiwan.
Indoxyl sulfate (IS) has been implicated in the pathogenesis of cardiovascular diseases. IS is converted from indole, a metabolite of dietary tryptophan through the action of gut microbial tryptophanase, by two hepatic enzymes: CYP2E1 and SULT1A1. We hypothesized that the effect of tryptophan intake on IS production might differ from person to person.
View Article and Find Full Text PDFBiol Pharm Bull
January 2025
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Enhanced inflammatory and immune responses have been observed in patients with major depressive disorder, pointing to anti-inflammatory substances as potential seeds for developing novel antidepressants. Omega-3 polyunsaturated fatty acid metabolites, such as resolvin D and E series, maresins, and protectins (collectively known as specialized pro-resolving mediators) demonstrate anti-inflammatory effects. This study examined the antidepressant-like effects of maresin-1 (MaR1) on lipopolysaccharide (LPS)-induced depression-like behaviors in mice.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Neuroscience, Laboratory of Prion Neurobiology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
There is no cure for Marinesco-Sjögren syndrome (MSS), a genetic multisystem disease linked to loss-of-function mutations in the SIL1 gene, encoding a BiP co-chaperone. Previously, we showed that the PERK kinase inhibitor GSK2606414 delays cerebellar Purkinje cell (PC) degeneration and the onset of ataxia in the woozy mouse model of MSS. However, GSK2606414 is toxic to the pancreas and does not completely rescue the woozy phenotype.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Computer Science and Technology, School of Computer Science, Northeast Electric Power University, Jilin, China.
Predicting Drug-Drug Interactions (DDIs) enables cost reduction and time savings in the drug discovery process, while effectively screening and optimizing drugs. The intensification of societal aging and the increase in life stress have led to a growing number of patients suffering from both heart disease and depression. These patients often need to use cardiovascular drugs and antidepressants for polypharmacy, but potential DDIs may compromise treatment effectiveness and patient safety.
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