Highly sensitive determination of α-lipoic acid in pharmaceuticals on a boron-doped diamond electrode
At a Glance
Section titled “At a Glance”| Metadata | Details |
|---|---|
| Publication Date | 2021-01-01 |
| Journal | Open Chemistry |
| Authors | Agata Skorupa, Sławomir Michałkiewicz, Magdalena Jakubczyk |
| Institutions | Jan Kochanowski University |
| Citations | 6 |
| Analysis | Full AI Review Included |
Executive Summary
Section titled “Executive Summary”This research details the development and validation of a highly sensitive differential pulse voltammetry (DPV) method for determining alpha-lipoic acid (LA) in pharmaceutical preparations using a Boron-Doped Diamond Electrode (BDDE).
- Core Achievement: Successful application of BDDE in a McIlvaine (citrate-phosphate, C-PB) buffer (pH 3.0) for LA determination, achieving superior sensitivity compared to most existing voltammetric and chromatographic methods.
- Performance: The method demonstrated an exceptionally low Limit of Detection (LOD) of 1.94 x 10-8 mol L-1 and a wide linear range (5.82 x 10-8 to 4.00 x 10-4 mol L-1).
- Electrochemical Mechanism: The anodic oxidation of LA on BDDE in this specific buffer is characterized as a quasi-reversible, diffusion-controlled, one-electron process, which enhances the analytical sensitivity.
- Analytical Reliability: High precision (RSD less than 1.2%) and accuracy (Recovery 99.1-100.5%) were confirmed, with results comparable to or better than the reference HPLC method.
- Practical Advantages: The procedure is simple, requires minimal sample preparation (dissolution only), avoids complex separation steps, and utilizes aqueous buffers, aligning with green chemistry principles.
- Matrix Effect Reduction: The DPV technique on BDDE effectively minimizes matrix interference, allowing direct analysis of complex pharmaceutical samples.
Technical Specifications
Section titled “Technical Specifications”| Parameter | Value | Unit | Context |
|---|---|---|---|
| Working Electrode | BDDE (3 mm) | Diameter | Used for primary measurements |
| Reference Electrode | Ag/AgCl (3 mol L-1 KCl) | N/A | Standard reference |
| Auxiliary Electrode | Platinum wire | N/A | Standard auxiliary |
| Optimal Buffer | McIlvaine (C-PB) | pH 3.0 | Citrate-Phosphate buffer |
| Ethanol Content | 4 | % (v/v) | Used to dissolve LA standard/samples |
| Peak Potential (Ep) | 0.885 | V vs Ag/AgCl | Anodic oxidation of LA (DPV) |
| DPV Pulse Amplitude (dE) | 40 | mV | Optimized DPV parameter |
| DPV Scan Rate (v) | 20 | mV s-1 | Optimized DPV parameter |
| Linearity Range (LR) | 5.82 x 10-8 to 4.00 x 10-4 | mol L-1 | Wide concentration range |
| Limit of Detection (LOD) | 1.94 x 10-8 | mol L-1 | High sensitivity achieved |
| Limit of Quantification (LOQ) | 5.82 x 10-8 | mol L-1 | Lowest quantifiable concentration |
| Correlation Coefficient (r) | 0.9999 | N/A | Calibration plot linearity |
| Repeatability (RSD) | 0.7 | % | For 1 x 10-4 mol L-1 LA (n=10) |
| Reproducibility (RSD) | 1.2 | % | Over 5 days (at 1 x 10-4 mol L-1 LA) |
| Recovery (Pharmaceuticals) | 99.1 to 100.5 | % | Accuracy check against declared values |
| Interference Tolerance | < 1.3 | % change in Ip | For 10-fold excess of B vitamins, glucose, Cl- |
Key Methodologies
Section titled “Key Methodologies”The determination of LA utilized Differential Pulse Voltammetry (DPV) on a BDDE in a specific aqueous buffer system.
- Electrode Activation (BDDE): The BDDE was activated daily using cyclic polarization in 1 mol L-1 HNO3. Polarization range was -1.6 V to 2.0 V (v = 0.1 V s-1) for 10 cycles, starting and finishing at negative potentials.
- Buffer Selection: Four buffers (Britton-Robinson, McIlvaine, Citrate, Acetate) were tested across various pH values. McIlvaine (Citrate-Phosphate, C-PB) buffer at pH 3.0 was selected as optimal due to maximum DPV peak current and excellent curve reproducibility.
- Solution Preparation: LA stock solution (1.84 x 10-2 mol L-1) and pharmaceutical samples were prepared in ethanol due to LA’s limited water solubility. Test solutions were diluted with the C-PB buffer, maintaining a constant 4% (v/v) ethanol concentration.
- Voltammetric Technique: DPV was employed using optimized parameters: pulse amplitude (dE) = 40 mV, pulse width (τ) = 60 ms, and scan rate (v) = 20 mV s-1.
- Quantification: The Multiple Standard Addition Method was used for pharmaceutical analysis. The peak current at 0.885 V vs Ag/AgCl was measured, and calibration curves were constructed based on the linear relationship between current and concentration.
- Comparative Analysis: High Performance Liquid Chromatography (HPLC) using a C-18 column and UV-Vis detection (332 nm) was used as the reference method for validation.
Commercial Applications
Section titled “Commercial Applications”The robust performance and high sensitivity of the BDDE sensor system make it highly valuable for analytical and quality control applications, particularly in regulated industries.
- Pharmaceutical Quality Control (QC): Routine, high-throughput analysis and quantification of alpha-lipoic acid (LA) content in various formulations (tablets, soft/hard capsules) without complex extraction or separation steps.
- Dietary Supplement Analysis: Accurate determination of LA in nutritional and dietary supplements, ensuring compliance with labeling standards.
- Green Analytical Chemistry: The method relies on aqueous buffers and minimal organic solvent consumption (only 4% ethanol), making it an environmentally friendly alternative to traditional HPLC.
- Electroanalytical Sensor Development: BDDE technology is ideal for developing highly stable and fouling-resistant sensors for biologically electroactive compounds, leveraging the electrode’s wide potential window and low background current.
- Clinical and Biological Monitoring: Potential application in monitoring LA and related antioxidants in complex biological matrices (e.g., serum or tissue extracts), given the BDDE’s resistance to deactivation.
View Original Abstract
Abstract A simple, highly sensitive, and selective differential pulse voltammetry method for the determination of α-lipoic acid (LA) in pharmaceutical preparations was developed and validated. The method is based on a quasi-reversible, diffusion-controlled, one-electron anodic oxidation of LA on a boron-doped diamond electrode (BDDE) in a McIlvaine (citrate-phosphate, C-PB) buffer solution at pH 3.0. For the first time, this environment was used for LA determination. A linear calibration curve was obtained within the concentration range 5.82 × 10 −8 to 4.00 × 10 −4 mol L −1 with a correlation coefficient of 0.9999. The limits of detection was estimated to be 1.94 × 10 −8 mol L −1 , which is one of the lowest values characteristic of voltammetric and chromatographic methods of LA determination. The proposed procedure is sensitive, accurate, and precise. Its utility was demonstrated in the determination of LA in pharmaceuticals without the need for its separation from the matrices. The results were comparable to those obtained by high performance liquid chromatography reference method and were in good accordance with the once declared by manufacturers. Thus, our method can be considered as an alternative to the dominant chromatographic determinations of α-LA in real samples.