Distribution of Fluvoxamine and Identification of the Main Metabolite in a Fatal Intoxication

Abstract

Fluvoxamine is a selective serotonin reuptake inhibitor, with a half-life of about 30 hours, that is commonly prescribed in the treatment of depression and obsessive and compulsive disorders. Though its more favorable adverse effect profile in comparison to tricyclic antidepressants, overdosages could lead to severe central nervous system depression. We hereby report the case of a 48-year-old woman with psychiatric disorders, who died in the Protected Community where she lived. An autopsy, during which multiorgan congestion and aspiration of gastric content were found, was performed 9 days after the death. Femoral and cardiac blood, urine and bile were collected for toxicological analysis. GC–MS, LC–MS-MS and LC–HRMS screenings were performed on blood samples. The analysis allowed to identify the following drugs: fluvoxamine, clotiapine, 7-aminoclonazepam, propranolol, gabapentin and haloperidol. Quantification of the detected drugs in blood was performed by means of a validated LC–MS-MS analytical procedure and the following results were achieved: fluvoxamine (2.20 mg/L), gabapentin (41.00 mg/L), 7-aminoclonazepam (0.24 mg/L), clotiapine (0.07 mg/L), haloperidol (<0.01 mg/L) and propranolol (0.24 mg/L). Fluvoxamine concentration in blood exceeded approximately 10 times the upper limit of therapeutic blood levels (0.23 mg/L). Contributory causes of death, due to multiple drugs use, however, cannot be excluded. The distribution of fluvoxamine in all biological fluids was evaluated and a postmortem redistribution effect was observed (C/P blood ratio: 1.86). Fluvoxamine acid metabolite was identified in urine, bile and in cardiac blood, through a LC–QTOF analytical procedure.

Recent Advances in Analytical Techniques for Antidepressants Determination in Complex Biological Matrices: A Review

“…Protein precipitation, 26,48,58,59 LLE, 15,25,29,41,46,53,60 SPE, 12,17,[20][21][22][23]28,32,34,36,42,51,56,59,62,64 and some miniaturized techniques-such as SPME, 33 MEPS, 30,50,54 DLLME, 14 AA-DLLME, 27 BAμE, 24 and LPME 13 are the most utilized procedures for extracting antidepressants from the biological samples.…”

“…As mentioned above, biospecimens where antidepressants are usually detected include urine, 24,51,53-55,61,64,65 whole blood, 11,17,22,23,29,31,35,36,39,41,57,58 dried blood spots, 11,32 plasma, 23,26,28,48,48,60,63 serum, 23,40,46,50,63,65 hair, 44,51 OF, 30,62,67 pericardial fluid, 14 bone marrow, 33,52,66 bones, 21,25,34,47,59 brain tissue, 36 intraosseous fluid, 26 meconium, 56 and VH 12,13 with each matrix requiring specific treatment depending on the type of antidepressant under investigation.…”

“…Vignali et al (2021) 64 employed GC/MS, LC/MS/MS and LC/Q-TOF to identify fluvoxamine a SSRI in biological fluids (cardiac and femoral blood, bile and urine) collected from a corpse. Fluvoxamine (2.20 mg/L) was quantified in blood using a validated LC-MS-MS method.…”

CYP2D6 gene polymorphism and apatinib affect the metabolic profile of fluvoxamine

“…Moreover, interactions between fluvoxamine and other drugs are frequently being reported. A study found one fatality in a woman who was taking clotiapine, 7-aminoclonazepam, propranolol, gabapentin and haloperidol alongside fluvoxamine developing antipsychotic malignant syndrome (Vignali et al, 2021). Interactions of fluvoxamine with antiepileptic or antidepressant drugs have also been issued (Mula and Trimble, 2003;Spina et al, 2016).…”