Skip to content

Fast and simple voltammetric sensing of avanafil in the pharmaceutical formulation by using unmodified boron-doped diamond electrode

MetadataDetails
Publication Date2024-06-27
JournalADMET & DMPK
AuthorsHoshyar Saadi Ali, Hemn A.H. Barzani, Yavuz Yardım
InstitutionsVan YĂŒzĂŒncĂŒ Yıl Üniversitesi, Lebanese French University
Citations5
AnalysisFull AI Review Included

This research details the development of a fast, simple, and highly sensitive voltammetric method for quantifying avanafil (AVN) using an unmodified Boron-Doped Diamond (BDD) electrode.

  • Core Value Proposition: The method eliminates the need for complex electrode modification, significantly simplifying the analytical process, reducing resource consumption, and enhancing feasibility compared to previous electrochemical studies.
  • Material and Technique: Unmodified BDD (1000 ppm B doping) was used as the working electrode, employing Square-Wave Voltammetry (SWV) for quantification.
  • Optimal Conditions: Analysis was performed in Britton-Robinson (BR) buffer (0.04 mol L-1) at pH 4.0, yielding a sharp, irreversible anodic peak at +1.33 V (vs. Ag/AgCl).
  • High Sensitivity: The method achieved a wide linear dynamic range of 1.0 to 62 ”mol L-1 and a low Limit of Detection (LOD) of 0.29 ”mol L-1.
  • Robustness and Precision: The method demonstrated good reproducibility with intra-day and inter-day Relative Standard Deviations (RSDs) of 5.6% and 7.2%, respectively.
  • Practical Application: Successful determination of AVN content in commercial pharmaceutical tablets (103.2 mg found vs. 100.0 mg labeled) and satisfactory recovery rates in spiked human urine samples (92.0% ± 4.3%).
ParameterValueUnitContext
Electrode MaterialBoron-Doped Diamond (BDD)N/AWorking electrode
Boron Doping Level1000ppmBDD specification
Electrode Diameter3mmBDD specification
Electroactive Surface Area0.036cm2Determined via prior study
Reference ElectrodeAg/AgCl (3 mol L-1 NaCl)N/ABAS Model RE-1
Optimal ElectrolyteBritton-Robinson Buffer (BR)0.04 mol L-1pH 4.0
Optimal Peak Potential (Ep)+1.33VSWV vs. Ag/AgCl
SWV Frequency (f)50HzOptimized parameter
SWV Step Potential (ΔEs)12mVOptimized parameter
SWV Pulse Amplitude (ΔEsw)60mVOptimized parameter
Linear Dynamic Range (LDR)1.0 to 62”mol L-1AVN concentration
Limit of Detection (LOD)0.29”mol L-1Calculated via 3s/m approach
Oxidation MechanismIrreversible AnodicN/AInvolves 1 electron and 1 proton
Intra-day Precision (RSD)5.6%Repeatability (0.5 ”g mL-1 AVN)
Inter-day Precision (RSD)7.2%Reproducibility (5 consecutive days)
Tablet Recovery103.2mgFound vs. 100.0 mg labeled (RSD 3.8%)

The experimental approach utilized cyclic voltammetry (CV) for mechanistic study and square-wave voltammetry (SWV) for quantification, focusing on optimizing parameters for the unmodified BDD electrode.

  1. Electrode Pretreatment:

    • The BDD electrode surface was activated daily using Anodic (APT) and Cathodic (CPT) pretreatment in 0.5 mol L-1 H2SO4.
    • Applied voltage range: +1.8 V to -1.8 V.
    • Cleaning Protocol: Gentle rubbing with a moist BAS polishing pad, followed by rinsing with deionized water to remove residual oxidation byproducts.
  2. Mechanistic Study (CV):

    • CV was performed in 0.04 mol L-1 BR buffer (pH 4.0) over a range of 0 to 1.70 V.
    • The oxidation was confirmed as irreversible (no cathodic peak on reverse scan).
    • Scan rate dependence analysis confirmed the process is influenced by both adsorption and diffusion effects (log Ip vs. log v slope ≈ 0.553).
    • The reaction mechanism was determined to involve a 1-electron, 1-proton transfer (n ≈ 1.24, based on Ep-Ep/2 analysis).
  3. Optimization (SWV):

    • The supporting electrolyte and pH were optimized, confirming 0.04 mol L-1 BR buffer at pH 4.0 provided the highest, sharpest peak current.
    • Instrumental parameters were optimized: frequency (50 Hz), step potential (12 mV), and pulse amplitude (60 mV).
  4. Sample Analysis:

    • Pharmaceuticals: Tablets were ground, dissolved in 0.1 mol L-1 HCl, and analyzed using the standard addition method in the optimized BR buffer.
    • Biological Fluids: Urine samples were spiked with AVN standard solution, diluted with BR buffer (pH 4.0), and analyzed directly using the standard addition method.

The use of unmodified Boron-Doped Diamond (BDD) electrodes for sensitive drug detection is highly relevant to industries requiring robust, stable, and chemically inert sensors.

  • Pharmaceutical Quality Control (QC): Direct, fast, and cost-effective quantification of active pharmaceutical ingredients (AVN) in fixed-dose formulations, providing an alternative to complex HPLC or UV-Vis methods.
  • Clinical and Forensic Diagnostics: Direct determination of drug concentrations (AVN) in biological fluids (like urine or plasma) without extensive sample preparation (extraction or filtration), leveraging BDD’s resistance to fouling by biological matrices (e.g., uric acid, dopamine).
  • Electrochemical Sensing and Manufacturing: BDD electrodes are ideal for industrial environments due to their wide electrochemical potential window, chemical inertness, and mechanical durability, making them suitable for continuous monitoring systems.
  • Drug Metabolism and Pharmacokinetics (DMPK) Studies: The high sensitivity and low LOD achieved allow for monitoring low concentrations of drugs or metabolites in research settings.
View Original Abstract

Background and purpose: Erectile dysfunction is a common issue among adult males involving difficulty in maintaining an erection, and it is often treated with fast-acting, low-side-effect drugs like avanafil (AVN), among other phosphodiesterase-5 inhibitors. Hence, developing fast, simple, and sensitive methods to detect AVN is crucial. Experimental approach: This study conducts an electroanalytical inquiry and provides a new voltammetric method for accurately analyzing AVN utilizing a boron-doped diamond (BDD) electrode without any modifications. Key results: In the Britton-Robinson buffer (BR, 0.04 mol L-1, pH 4.0), cyclic voltam­metry showed a clearly defined and irreversible anodic peak at around +1.44 V relative to Ag/AgCl. The pH of the solution was shown to have an impact on the voltammetric signals of the oxidation peaks. A good linear response for AVN quantification was achieved using square-wave voltammetry. This was done in a 0.04 mol L-1 BR (pH 4.0) solution at a potential of +1.33 V (vs. Ag/AgCl). The method exhibited a wide dynamic range of 0.5 to 30.0 Όg mL-1 (1.0 to 62 ”mol L-1) and a low limit of detection of 0.14 Όg mL-1 (0.29 ”mol L-1). The method proposed demonstrated suitability for determining AVN content in pharmaceutical formulations. The accuracy of the approach was demonstrated by comparing the results obtained using the developed method with those achieved using the UV-Vis spectrometry method. Conclusion: Our method simplifies the analytical process by eliminating the need for electrode modification, reducing both time and resource requirements while enhancing overall feasibility.