Evaluation of direct and indirect photodegradation of mianserin with high-performance liquid chromatography and short-term bioassays.

The widespread use of pharmaceuticals has lead to their detection in surface and ground waters. In the last year antidepressants in particular have shown very high growth dynamics of consumption and numerous research shows that these pharmaceuticals are detected in the environment and even in drinking water. Drugs and their metabolites can be subject to two types of photoreaction, direct and indirect photodegradation. These pharmaceuticals even at low concentration can have adverse effects on aquatic life, and the resulting photoproducts can be more toxic than parents compounds. The aim of this study was to evaluate the direct and indirect photodegradation of mianserin. The kinetics of the process and the identification of photoproducts were investigated by HPLC-PDA and HPLC-MS/MS, respectively. Ecotoxicity of mianserin before and after irradiation was assessed with a battery of assays with bacteria, protozoa and crustacea. The results show that mianserin was not toxic to Vibrio fischeri (Microtox), but its toxicity to protozoan Spirostomum ambiguum (Spirotox) and crustacean Thamnocephalus platyurus (Thamnotoxkit F(™)) was comparable to other antidepressants. On the basis of the results of the toxicity and HPLC before and after irradiation it can be seen that the decrease toxicity of mianserin was related only to a decrease of its concentration. The photoproducts had no impact to toxicity. The direct photodegradation of mianserin was more effective in UV/vis light than vis light. However the presence of humic acid in the indirect photodegradation increases the rate of degradation without regard to the kind of used light.

Planned complex suicide involving combined drug intoxication and femoral catheterization.

Complex planned suicide is characterized by the simultaneous use of two or more methods to ensure that death occurs even if one method fails. The authors present an original combination of two self-killing methods. A 42-year-old cardiologist, with a major depressive syndrome and several suicide attempts, as well as cocaine addiction, was found dead at his home with a femoral catheter inserted in the right femoral artery. The autopsy concluded that death was due to major hemorrhagic process in a context of suicide. Toxicological analyses, performed in peripheral blood by gas chromatography coupled to mass spectrometry and by liquid chromatography-diode array detection, revealed the presence of ethanol (0.13 g/L), cocaine, and metabolites (cocaine: 432 µg/L, benzoylecgonine: 3286 µg/L, ecgonine methyl ester: 1195 µg/L, cocaethylene: 41 µg/L), a potentially lethal concentration of citalopram (1.03 mg/L), toxic concentrations of hydroxyzine (0.11 mg/L), bromazepam (2.06 mg/L), and lidocaine (7.30 mg/L). At the end of these analyses, the death was reclassified as planned complex suicide combining drug intoxication and catheterization of the femoral artery. The authors discuss the main aspects of this case and stress the importance of meticulous analysis of all available evidence: witness reports, victim's medical history and occupation, findings of at-the-scene examination, autopsy, and toxicological analyses, in order to exclude homicide and to understand the sequence of events that led to death.

Comparative study on photocatalytic degradation of the antidepressant trazodone using (Co, Fe and Ru) doped titanate nanowires: Kinetics, transformation products and in silico toxicity assessment.

Titanate nanomaterials have been outstanding in the removal of emerging contaminants by the photocatalysis process. These photocatalysts, when modified through techniques such as doping with metals, they have advantages over TiO2, especially in the region of visible light. In this work, the photocatalytic performance of four recent reported catalysts, pristine titanate nanowires, cobalt-doped titanate nanowires, iron-doped titanate nanowires and ruthenium-doped titanate nanowires, for the removal of the antidepressant trazodone under visible light radiation was compared. The iron-doped titanate nanowires presented the best catalytic activity by the catalyst surface area. Additionally, thirteen transformation products (TPs) were identified by high-resolution mass spectrometry and, to the best of our knowledge, nine of them have never been described in the literature. It was shown that for each catalyst different TPs were formed with distinct time profiles. Finally, toxicity assessment by computational methods showed that TPs were not readily biodegradable and they presented toxicity to aquatic organisms with mutagenic potential. These findings reinforce the importance of taking into consideration the TPs formed during the removal of pollutants since many of them may be toxic and can be produced during photocatalysis.

Photoisomerization of fluvoxamine generates an isomer that has reduced activity on the 5-hydroxytryptamine transporter and does not affect cell proliferation.

Fluvoxamine, a selective serotonin re-uptake inhibitor, is used as antidepressant/anxiolytic. The presence of a C=N double bond in the structure of fluvoxamine implies the existence of two geometric isomers: E- (trans) and Z- (cis), and suggests the hypothetical susceptibility of the molecule to photoisomerization. Clinically effective fluvoxamine is in its trans form. UVB (ultraviolet light, class B, wavelength range 290-320 nm) irradiation of aqueous solutions of fluvoxamine generated a photoproduct, which was isolated and analyzed by nuclear magnetic resonance (NMR) and mass spectrometry (MS), and identified as the cis isomer of fluvoxamine. This cis-isomer lost capacity to inhibit serotonin uptake, suggesting that light exposure might reduce the clinical efficacy of fluvoxamine. Alternatively, the photoproduct could be used as an inactive isomer in the studies of antidepressant mechanisms. Recent proposal suggests that antidepressants increase neurogenesis in the adult brain, whereas either an inhibitory or a stimulatory action of antidepressants on [(3)H]thymidine uptake in vitro has been attributed to their interaction with serotonergic mechanisms. Lower concentrations (i.e., 2 microM) of fluvoxamine and fluoxetine (another selective serotonin re-uptake inhibitor) stimulated [(3)H]thymidine uptake in mature, but inhibited it in immature cultures of rat cerebellar granule cells; the photoproduct was ineffective. A high concentration of fluvoxamine (i.e., 20 microM) but not the photoproduct was toxic to both immature and mature cultures. We suggest that a mechanism sensitive to fluvoxamine photoisomerization might be involved in the action of antidepressants on cell proliferation.