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

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 ~10 times the upper limit of therapeutic blood levels (0.23 mg/L). Contributory causes of death, such as due to multiple drug 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 an LC-QTOF analytical procedure.

Delta-9-tetrahydrocannabinolic acid A (THC-A) in urine of a 15-month-old child: A case report.

INTRODUCTION: The acidic forms of cannabinoids, THC-A and CBD-A are naturally present in cannabis plants and preparations and are generally decarboxylated to the active compounds before the use (e.g. thermally decarboxylated through smoking). Hence, the identification of the acidic compounds in urine could be an evidence of cannabis ingestion rather than a passive exposure to smoke. This case report described a 15-month-old child that suffered an acute intoxication by accidental cannabis ingestion. It is important to assess the ingestion and to discriminate it from a passive exposure to better interpret the clinical findings and to establish the correct therapeutic procedure. METHODS: Urine samples were simply diluted in deionized water and directly injected in the LC-MS/MS system. D3-THCCOOH was used as internal standard. Chromatographic separation of THCCOOH, THC-A and CBD-A was carried out in reversed phase on a c18 column. A triple quad in MRM negative mode was used to monitor the three analytes. RESULTS AND DISCUSSION: The developed LC-MS/MS method was simple and fast. A LOD of 3.0ng/mL and a LOQ of 10.0ng/mL were measured for the three compounds. The analytical procedure was validated accordingly to international guidelines. The two urine samples collected from the 15-month-old child at the hospitalization and after three days provided positive results for THCCOOH (130.0 and 10.0ng/mL respectively). THC-A was found only in the urine sample collected at the hospitalization (concentration: 70.0ng/mL). CONCLUSION: THC-A was detected and quantitated in a urine sample of a 15-month-old child.