Monitoring of the electrochemical oxidation of venlafaxine and its metabolite o-desmethylvenlafaxine using a flow cell and high-resolution mass spectrometry
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2025-07-10 |
| Journal | Environmental Sciences Europe |
| Authors | Melanie Voigt, Jean-Michel Dluziak, Nils Wellen, Victoria Langerbein, Martin Jaeger |
| Institutions | Hochschule Niederrhein |
| Citations | 1 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive Summaryâ- Core Achievement: Successful monitoring and optimization of the electrochemical advanced oxidation (EAOP) of the antidepressant venlafaxine and its metabolite (o-desmethylvenlafaxine) using a Boron-Doped Diamond (BDD) flow cell.
- Product Identification: High-Resolution Mass Spectrometry (HRMS) confirmed five transformation products (TPs) for venlafaxine and four newly elucidated TPs for o-desmethylvenlafaxine.
- Mechanism Elucidation: Mechanistic studies, including the use of tert-butanol as a radical scavenger, confirmed that the indirect mechanism (oxidation via hydroxyl radicals, HO) is the dominant degradation pathway.
- Optimal Conditions: Best elimination efficiency for both drugs was achieved at an acidic pH (pH 3) and an oxidation potential of 1.5 V.
- Ecotoxicity Assessment: In silico Quantitative Structure-Activity Relationship (QSAR) analysis showed that the TPs formed via the indirect hydroxyl radical mechanism generally possess lower ecotoxicity than the parent drug substance.
- Industrial Relevance: The study validates BDD-EAOPs as a highly suitable and environmentally beneficial technology for advanced purification stages in wastewater treatment, particularly for eliminating EU watchlist pharmaceuticals.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Working Electrode Material | Boron-Doped Diamond (BDD) | N/A | Anode material for oxidation |
| Boron Doping Level | 6000 to 8000 | ppm | BDD electrode specification |
| Optimal Oxidation Potential | 1.5 | V | Voltage yielding best elimination and intermediate formation |
| Optimal pH Range | 3 | N/A | Favorable for strong product formation and high degradation efficiency |
| Hydroxyl Radical Potential (HO) | 2.8 | V | High standard oxidation-reduction potential |
| Electrochemical Oxidation Transfer Reaction (EOTR) Threshold | > 1.23 | V | Voltage required for water discharge and HO generation |
| Flow Cell Velocity | 50 | ”L/min | Continuous sample throughput rate |
| Cell Scan Rate (Mass Voltammograms) | 5 | mV/s | Rate of potential increase during monitoring |
| HRMS Resolution (MS1) | 60,000 | N/A | Resolution for accurate mass measurement |
| HRMS Resolution (MS3) | 60,000 | N/A | Resolution for fragmentation analysis |
| Venlafaxine Initial Concentration | 20 ± 2 | mg/L | Input concentration for flow cell experiments |
| o-desmethylvenlafaxine Initial Concentration | 20 ± 6 | mg/L | Input concentration for flow cell experiments |
| Venlafaxine Residue (pH 3, H2SO4) | 27 | % | Remaining drug substance at 3.5 V (higher efficiency than formic acid) |
Key Methodologies
Section titled âKey Methodologiesâ- Solution Preparation and pH Control: Solutions of venlafaxine or o-desmethylvenlafaxine (approx. 20 mg/L) were prepared in ultrapure water. pH was adjusted using formic acid, sulfuric acid (for comparison), or ammonia, covering a range of pH 3 to 9.
- Electrochemical Flow Cell Setup: Experiments were conducted using a ROXY⹠system featuring a ”PrepCell flow cell and a potentiostat. The working electrode was a BDD anode (6000-8000 ppm B).
- Continuous Flow Operation: Solutions were continuously pumped through the flow cell at a rate of 50 ”L/min, allowing for rapid and continuous product formation studies.
- Mass Voltammogram Acquisition: Mass spectra were recorded while the oxidation potential was ramped from 0 to 3500 mV at 5 mV/s. This technique correlated product formation intensity directly with the applied voltage.
- Mechanistic Study (Scavenging): Tert-butanol (10% and 30%) was added to solutions to scavenge hydroxyl radicals (HO), thereby confirming the dominance of the indirect oxidation mechanism.
- Structural Elucidation (HPLC-HRMS): Collected samples were analyzed using Ultra-High-Performance Liquid Chromatography (UHPLC) coupled to a high-resolution Orbitrap mass spectrometer (HRMS). Fragmentation (MS2 and MS3) was performed using Higher-Energy Collision-Induced Dissociation (HCD) at 30 eV and 45 eV.
- Ecotoxicity Prediction (QSAR): In silico ecotoxicity assessment was performed on all identified parent compounds and TPs using the QSAR Toolbox (v4.4.1) and the ECOSAR model (Aliphatic Amines 1.0 class) to predict acute (LC50, EC50) and chronic toxicity (ChV).
Commercial Applications
Section titled âCommercial Applicationsâ- Advanced Wastewater Treatment: Direct application as a tertiary or quaternary purification stage in municipal and industrial WWTPs to eliminate persistent organic pollutants (POPs) and pharmaceuticals, especially those listed on the EU watchlist.
- Water Reuse and Recycling: Utilizing BDD-EAOPs for the robust removal of trace contaminants in water intended for industrial, agricultural, or indirect potable reuse.
- BDD Electrode Technology: Drives demand for specialized, high-performance BDD anodes optimized for high current density and efficient HO radical generation, crucial for maximizing mineralization rates.
- Pharmaceutical Effluent Management: Targeted treatment of concentrated waste streams from pharmaceutical manufacturing, where high concentrations of parent drugs and metabolites require complete destruction prior to discharge.
- Environmental Risk Assessment Services: Integration of flow cell EAOP testing and QSAR analysis into regulatory compliance and environmental impact studies for new chemical substances and drug candidates.
View Original Abstract
Abstract Background The antidepressant venlafaxine and its metabolite o -desmethylvenlafaxine are frequently found in water bodies around the world reaching several micrograms per liter. As a remedy, electrochemical advanced oxidation processes (EAOPs) such as anodic oxidation with a boron-doped diamond (BDD) electrode have proven to be a suitable means to prevent entrance in the aquatic environment. For potential application, optimization of the EAOPs can be readily achieved by variation of the conditions using a flow cell as compared to a batch-mode cell. Monitoring and characterization of the reactants provide inside into the oxidation mechanism. Results High-performance liquid chromatography and high-resolution mass spectrometry led to the observation of five transformation products of venlafaxine and to four of o -desmethylvenlafaxine. Mass voltammograms were recorded from which the impact of the oxidation conditions on the degradation and the quantity and nature of transformation products were derived. The transformation pathways were identified as well. Detailed analysis revealed that hydroxyl radicals played the major role in the electrochemical oxidation of venlafaxine and o -desmethylvenlafaxine. The prevalence of the hydroxyl radical induced degradation was further corroborated by the radical scavenger tert -butanol, causing a decrease in elimination efficiency. Both drugs were best eliminated at pH 3 and a voltage of 1.5 V, with the least ecotoxicological concern as indicated by QSAR analysis. Conclusion The study shall contribute to the advancement of EAOPs for advanced stages in wastewater purification treatment. An in silico ecotoxicity assessment using QSAR analysis showed that electrochemical oxidation is beneficial from an ecotoxicological point of view. Especially products formed via the indirect hydroxyl radical-induced mechanism showed a lower ecotoxicity than the initial compound. Graphical Abstract