Comparison of Chemical and Electrochemical Approaches to Abacavir Oxidative Stability Testing

At a Glance

Metadata	Details
Publication Date	2023-03-03
Journal	Sensors
Authors	Lucie Pražáková, Jan Fischer, Andrew Taylor, Anna Kubíčková
Institutions	Czech Academy of Sciences, Institute of Physics, Czech Academy of Sciences
Citations	6
Analysis	Full AI Review Included

Technical Documentation & Analysis: Electrochemical Stability Testing using BDD

Executive Summary

This documentation analyzes the application of Boron-Doped Diamond (BDD) electrodes in accelerating pharmaceutical forced degradation studies, specifically focusing on the oxidative stability testing of Abacavir. The research validates BDD as a superior material for rapid, controlled electrochemical oxidation compared to traditional chemical methods (hydrogen peroxide).

Speed Advantage: Electrochemical oxidation achieved the required 20% Abacavir degradation in less than 10 minutes (4-7 minutes optimal), drastically reducing the time required compared to chemical oxidation (hours, even at elevated temperatures).
Material Superiority: BDD electrodes demonstrated a wider potential window and greater resistance to passivation than conventional platinum (Pt) electrodes, enabling oxidation in the high-potential “radical region” (up to +4.00 V).
Product Consistency: Electrochemical methods produced the same primary degradation products (OP1, OP2) as chemical methods, but generated a more complete profile (both OP1 and OP2 formed simultaneously), offering a more accurate prediction of long-term API stability.
Optimal Parameters: Fastest degradation was achieved using BDD at a potential of +4.00 V and an electrolyte pH of 9.0.
6CCVD Value Proposition: 6CCVD specializes in custom BDD materials, ensuring researchers can obtain the precise doping levels (e.g., 4000 ppm B/C ratio) and dimensions (up to 125mm wafers) required for high-throughput, reproducible pharmaceutical stability testing systems.

Technical Specifications

The following table summarizes the critical hard data points and performance metrics extracted from the research paper, highlighting the conditions achieved using BDD and Platinum electrodes.

Parameter	Value	Unit	Context
BDD Electrode B/C Ratio	4000	ppm	Working electrode specification
BDD Electrode Area	0.20	cm²	Working electrode dimension
Optimal BDD Potential (Fastest)	+4.00	V	For fastest degradation rate
Optimal BDD Potential (15% Deg.)	+3.00	V	For controlled pharmaceutical stability testing
Optimal Pt Potential (Max)	+1.15	V	Limited by potential window edge
Electrolyte Concentration	0.20	mol L^-1	Ammonium acetate buffer
Optimal pH for Oxidation	9.0	N/A	Fastest degradation rate on both BDD and Pt
Time to 15% Degradation (BDD, pH 9.0)	4-5	min	Electrochemical method (Fastest)
Time to 15% Degradation (Pt, pH 7.0)	6-7	min	Electrochemical method
Time to 15% Degradation (H₂O₂, 50 °C)	<2	hours	Chemical method (Accelerated)
Degradation Product OP1 m/z	319.20	Da	Identified by UHPLC/MS
Degradation Product OP2 m/z	246.90	Da	Identified by UHPLC/MS
RSD of Abacavir Peak Area (Pt)	3.5	%	Repeatability of oxidation process (5 runs)
RSD of Abacavir Peak Area (BDD)	~5	%	Repeatability of oxidation process (5 runs)

Key Methodologies

The electrochemical degradation process relied on precise control of material properties and operational parameters, particularly for the Boron-Doped Diamond (BDD) working electrode.

Electrode Preparation:
- BDD: Circular electrode (0.20 cm²) with a Boron/Carbon (B/C) ratio of 4000 ppm.
- Platinum: Large-area platinum mesh (geometric area 53 cm²) used for comparison.
- Cleaning: BDD was anodically cleaned using sulfuric acid (c = 0.50 mol L^-1) for 10 min at +2.5 V (three-electrode) or +4.5 V (two-electrode) before each measurement. Platinum was cleaned via annealing in an upper reducing flame for 3 min.
Electrochemical Setup:
- Cell Type: Glass batch cells (25 mL for Pt, 1 mL for BDD).
- Electrolyte: 0.20 mol L^-1 ammonium acetate buffer, adjusted to pH 4.0, 7.0, or 9.0.
- Reference Electrode: Ag|AgCl|3.00 mol L^-1 KCl (for potentials up to +2.50 V).
- Auxiliary Electrode: Platinum counter electrode.
- Power Source: Potentiostat (for < +2.50 V) or Owon P4603 power supply (for > +2.50 V, specifically for BDD radical region testing).
Oxidation Parameters:
- Target Degradation: 15-20% loss of Active Pharmaceutical Ingredient (API).
- Optimal Potentials: +1.15 V (Pt) and +4.00 V (BDD).
- Analysis: Oxidized solutions (200 µL aliquots) were analyzed using Ultra-High Performance Liquid Chromatography with Mass Spectrometry (UHPLC/MS).

6CCVD Solutions & Capabilities

The successful implementation of accelerated electrochemical stability testing hinges entirely on the quality and precise specification of the Boron-Doped Diamond (BDD) electrode. 6CCVD is uniquely positioned to supply the materials necessary to replicate and advance this critical research.

Applicable Materials

To replicate or extend the high-performance electrochemical oxidation demonstrated in this paper, researchers require highly conductive, robust Boron-Doped Diamond (BDD).

Recommended Material: Heavy Boron Doped PCD (Polycrystalline Diamond).
- Justification: The paper utilized a B/C ratio of 4000 ppm. 6CCVD offers PCD with heavy boron doping (typically > 3000 ppm) necessary to achieve the wide potential window and high conductivity required for radical-region oxidation (up to +4.00 V).
Alternative Material (For Micro-Sensors): Boron-Doped SCD (Single Crystal Diamond).
- Justification: While PCD is cost-effective for larger electrodes, SCD offers superior surface uniformity (Ra < 1nm) and crystal quality, ideal for highly sensitive micro-electrochemical arrays or flow-through cells where precise, repeatable surface kinetics are paramount.

Customization Potential

The research utilized a specific 0.20 cm² circular BDD electrode. 6CCVD’s custom fabrication capabilities ensure seamless integration into existing or novel electrochemical setups.

Requirement in Paper	6CCVD Customization Capability	Technical Advantage
Specific Doping Level	Custom B/C ratios available (e.g., 4000 ppm match).	Ensures optimal conductivity and wide potential window for radical generation.
Electrode Dimensions	Custom plates/wafers up to 125mm; precision laser cutting for specific geometries (e.g., 0.20 cm² discs).	Allows for scaling up or miniaturization of batch cells and flow-through systems.
Surface Finish	Polishing to Ra < 5nm (PCD) or Ra < 1nm (SCD).	Minimizes surface passivation and enhances repeatability (RSD of 3.5-5% achieved in the study).
Integration/Metalization	Internal capability for Au, Pt, Ti, W, etc., metalization.	Facilitates robust electrical contact and integration into complex three-electrode or two-electrode systems.

Engineering Support

The successful application of BDD in this study depended on careful selection of the working potential (+4.00 V) and electrolyte pH (9.0). 6CCVD recognizes that optimizing these parameters for new APIs requires deep material expertise.

6CCVD’s in-house PhD team can assist with material selection, doping level optimization, and surface preparation protocols for similar Pharmaceutical Forced Degradation and Stability Testing projects. We provide consultation on how BDD’s unique properties—such as its resistance to fouling and its ability to generate hydroxyl radicals—can be leveraged to accelerate stress studies for novel Active Pharmaceutical Ingredients (APIs).

For custom specifications or material consultation, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

A novel electrochemical approach using two different electrode materials, platinum and boron-doped diamond (BDD), was employed to study the oxidative stability of the drug abacavir. Abacavir samples were subjected to oxidation and subsequently analysed using chromatography with mass detection. The type and amount of degradation products were evaluated, and results were compared with traditional chemical oxidation using 3% hydrogen peroxide. The effect of pH on the rate of degradation and the formation of degradation products were also investigated. In general, both approaches led to the same two degradation products, identified using mass spectrometry, and characterised by 319.20 and m/z 247.19. Similar results were obtained on a large-surface platinum electrode at a potential of +1.15 V and a BDD disc electrode at +4.0 V. Degradation of 20% of abacavir, the rate required for pharmaceutical stability studies, took only a few minutes compared to hours required for oxidation with hydrogen peroxide. Measurements further showed that electrochemical oxidation in ammonium acetate on both types of electrodes is strongly pHdependent. The fastest oxidation was achieved at pH 9. The pH also affects the composition of the products, which are formed in different proportions depending on the pH of the electrolyte.

Tech Support

Original Source

DOI: https://doi.org/10.3390/s23052776

References

2012 - Current trends in forced degradation study for pharmaceutical product development
2016 - Forced degradation studies
2007 - Development and validation of a reverse-phase liquid chromatographic method for assay and related substances of abacavir sulfate [Crossref]
2018 - Forced degradation studies: Regulatory guidance, characterization of drugs, and their degradation products—A review
2012 - Stability testing of pharmaceutical products
2011 - How to approach a forced degradation study
2022 - Forced Degradation—A Review
2021 - Forced degradation study—A new approach for stress testing of drug substances and drug products