Voltammetric measurement of catechol-O-methyltransferase inhibitor tolcapone in the pharmaceutical form on the boron-doped diamond electrode
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2024-02-21 |
| Journal | TURKISH JOURNAL OF CHEMISTRY |
| Authors | Musa Kıran, Yavuz Yardım |
| Institutions | Czech Academy of Sciences, Institute of Analytical Chemistry |
| Citations | 3 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis study details the development and validation of a rapid, cost-effective electroanalytical method for measuring the Parkinsonâs drug Tolcapone (TOL) in pharmaceutical forms using a Boron-Doped Diamond (BDD) electrode.
- Core Technology: Square Wave Voltammetry (SWV) was successfully applied using a Cathodically Pretreated BDD (CPT-BDD) electrode, which significantly enhanced sensitivity and electron transfer kinetics compared to other pretreatment methods.
- Performance: The method achieved a wide linear working range (LWR) of 1.0-50.0 ”g mL-1 and a low Limit of Detection (LOD) of 0.29 ”g mL-1.
- Mechanism: TOL oxidation was found to be an irreversible, diffusion-controlled process, highly dependent on pH, suggesting a two-electron, two-proton (2e/2H+) transfer mechanism leading to the formation of o-quinone.
- Selectivity: The CPT-BDD electrode demonstrated excellent selectivity against common inorganic ions and filler materials (sugars, cellulose, starch) found in tablets.
- Real-World Application: The method was applied directly to commercial tablet samples without complex extraction or filtration, yielding high recovery rates (103.2% to 106.2%), confirming its practical reliability.
- Advantage: This voltammetric approach offers advantages over traditional chromatographic methods (HPLC, HPLC-MS/MS) in terms of simplicity, speed, and minimal use of hazardous organic solvents.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Working Electrode Material | Boron-Doped Diamond (BDD) | N/A | Boron content: 1000 ppm; Diameter: 3 mm |
| Optimal Supporting Electrolyte | Phosphate Buffer Solution (PBS) | 0.1 mol L-1 | Optimal pH 2.5 |
| Optimal SWV Frequency (f) | 100 | Hz | Square Wave Voltammetry parameters |
| Optimal Step Potential (ÎEs) | 12 | mV | Square Wave Voltammetry parameters |
| Optimal Pulse Amplitude (ÎEsw) | 60 | mV | Square Wave Voltammetry parameters |
| Optimal Anodic Peak Potential (SWV) | +0.66 | V (vs. Ag/AgCl) | TOL oxidation peak |
| Linear Working Range (LWR) | 1.0-50.0 | ”g mL-1 | Equivalent to 3.7 x 10-6 - 1.8 x 10-4 M |
| Limit of Detection (LOD) | 0.29 | ”g mL-1 | Calculated using 3 s/m formula |
| Correlation Coefficient (r) | 0.9984 | N/A | Linear regression equation (LRE) |
| Intra-day Repeatability (RSD) | 5.8 | % | For 1.0 ”g mL-1 TOL (n=10) |
| Inter-day Repeatability (RSD) | 7.1 | % | For 1.0 ”g mL-1 TOL (n=3) |
| Recovery in Tablets | 103.2 ± 2.2 to 106.2 ± 2.7 | % | Standard addition method |
| pH Dependence Slope (Ep vs. pH) | -0.053 | V/pH | Indicates 2e/2H+ oxidation process |
Key Methodologies
Section titled âKey MethodologiesâThe electroanalytical procedure utilized a three-electrode glass cell system (10 mL volume) at room temperature, employing a Platinum wire auxiliary electrode, an Ag/AgCl reference electrode, and the BDD working electrode.
- BDD Pretreatment (Initial): Before the start of each experimental day, the BDD electrode was subjected to a cathodic voltage of -1.8 V for 180 s in 0.5 mol L-1 H2SO4 solution to ensure a clean surface.
- BDD Pretreatment (Optimal CPT): Before each individual measurement, the electrode underwent Cathodic Pretreatment (CPT) at -1.8 V for 60 s in 0.5 mol L-1 H2SO4. This CPT procedure was found to yield the most sensitive results for TOL analysis.
- Cyclic Voltammetry (CV) Analysis: CV was used to study the electrochemical behavior of TOL (150 ”g mL-1) in 0.1 mol L-1 PBS (pH 2.5). The oxidation was determined to be irreversible and diffusion-controlled based on the linear relationship between anodic peak current (ipa) and the square root of the scan rate (v1/2).
- Supporting Electrolyte Optimization: SWV was performed across a pH range (2.0-7.0) using Britton-Robinson (BR) buffer. The optimal medium was determined to be 0.1 mol L-1 PBS at pH 2.5, yielding the highest signal intensity.
- SWV Parameter Optimization: The SWV technique was optimized for maximum sensitivity, resulting in the following parameters: frequency (f) = 100 Hz, step potential (ÎEs) = 12 mV, and pulse amplitude (ÎEsw) = 60 mV.
- Tablet Sample Preparation: Commercial tablets (100 mg TOL) were pulverized, dissolved in ethanol (25.0 mg equivalent in 25 mL), and stirred for 15 min. The resulting solution was analyzed directly in the voltammetric cell using the standard addition method.
Commercial Applications
Section titled âCommercial ApplicationsâThe use of the BDD electrode combined with SWV provides a robust platform suitable for various engineering and industrial applications:
- Pharmaceutical Quality Control (QC): Provides a rapid, simple, and affordable alternative to expensive HPLC or mass spectrometry methods for routine QC and quantification of active pharmaceutical ingredients (APIs) like Tolcapone in solid dosage forms.
- Electrochemical Sensor Development: BDDâs chemical inertness, wide potential window, and resistance to fouling make it an ideal material for developing highly stable and reusable amperometric sensors for organic molecules.
- Clinical Diagnostics and Bioavailability: The methodology is relevant for future development of sensors capable of monitoring drug levels (TOL) and related metabolites (like dopamine, uric acid, ascorbic acid) in biological fluids, crucial for pharmacokinetic studies.
- Advanced Carbon Materials Engineering: Confirms the utility of boron-doped diamond films (often produced via CVD) as high-performance working electrodes in complex chemical matrices, extending its use beyond traditional environmental applications.
- Process Analytical Technology (PAT): The speed and simplicity of SWV allow for potential integration into manufacturing lines for real-time monitoring of drug concentration during production.
View Original Abstract
This study presents an electroanalytical approach to measure the catechol-O-methyltransferase (COMT) inhibitor tolcapone (TOL) using a boron-doped diamond (BDD) electrode. The application of cyclic voltammetry (CV) technique revealed that TOL exhibited a distinct, diffusion-controlled, irreversible anodic peak at a potential of approximately +0.71 V (vs. Ag/AgCl) in a 0.1 mol L<sup>-1</sup> phosphate buffer solution (PBS) with a pH of 2.5. The oxidation of TOL is highly dependent on the pH and supporting electrolytes. Based on the data obtained from the pH investigation, a proposed mechanism for the electro-oxidation of TOL is suggested. Using the square wave voltammetry (SWV) technique, a satisfactory linear relationship was observed at approximately +0.66 V in a 0.1 mol L<sup>-1</sup> PBS with a pH of 2.5. The presented method exhibited linearity within the concentration range between 1.0-50.0 ÎŒg mL<sup>-1</sup> (3.7 Ă 10<sup>-6</sup>-1.8 Ă 10<sup>-4</sup> mol L<sup>-1</sup>), with a limit of detection (LOD) of 0.29 ÎŒg mL<sup>-1</sup> (1.1 Ă 10<sup>-6</sup> mol L<sup>-1</sup>). The BDD electrode demonstrated good selectivity against inorganic ions and filler materials interference. Finally, the suitability of the developed approach was assessed by measuring TOL in tablet formulations, resulting in favorable recoveries ranging from 103.4% to 106.2%.