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Electrochemical determination of antiviral drug Famciclovir in human serum samples at boron-doped diamond electrode

MetadataDetails
Publication Date2022-06-21
JournalTurkish Journal of Analytical Chemistry
AuthorsÇiğdem KanbeƟ Dindar
Citations2
AnalysisFull AI Review Included

This research details the development of a highly sensitive and eco-friendly electrochemical method for quantifying the antiviral drug Famciclovir (FCV) in human serum using a Boron-Doped Diamond Electrode (BDDE).

  • Core Value Proposition: The method offers a simple, rapid, and cost-effective alternative to traditional chromatographic techniques (HPLC/UPLC-MS/MS) for Therapeutic Drug Monitoring (TDM), eliminating time-consuming sample preparation steps like extraction and evaporation.
  • Electrode Material: BDDE was selected for its superior properties, including high chemical inertness, wide electrochemical potential range, and stability, avoiding the need for complex nanomaterial modifications.
  • Mechanism: The oxidation of Famciclovir at the BDDE surface was determined to be an irreversible, diffusion-controlled process, optimized in pH 4.7 Acetate Buffer Solution (ABS).
  • High Sensitivity: The method achieved very low limits of detection (LOD) for standard solutions (0.022 ”M) and applicable sensitivity for complex human serum matrices (0.42 ”M).
  • Quantification Technique: Differential Pulse Voltammetry (DPV) provided excellent linearity across relevant concentration ranges for both standard drug solutions (0.5-12 ”M) and spiked human serum (6-100 ”M).
  • Green Chemistry: The technique aligns with green analytical chemistry principles due to minimal solvent use and simple electrode preparation.

The following table summarizes the key operational parameters and analytical performance metrics achieved using the DPV method at the BDDE.

ParameterValueUnitContext
Working ElectrodeBoron-Doped Diamond (BDDE)3 mm diameterUnmodified surface
Optimal Supporting ElectrolyteAcetate Buffer Solution (ABS)0.1 MpH 4.7
Standard Linear Dynamic Range (LDR)0.5-12”MStandard FCV solution
Serum Linear Dynamic Range (LDR)6-100”MSpiked human serum
Standard Limit of Detection (LOD)0.022”MCalculated (3s/m)
Serum Limit of Detection (LOD)0.42”MCalculated (3s/m)
Standard Limit of Quantification (LOQ)0.066”MCalculated (10s/m)
Serum Limit of Quantification (LOQ)1.38”MCalculated (10s/m)
Anodic Peak Potential (Standard)1206mVDPV measurement
Anodic Peak Potential (Serum)1210mVDPV measurement
Diffusion Control Slope (log Ip vs log v)0.48N/AConfirms diffusion control (Theoretical 0.5)
DPV Step Potential10mVOptimized DPV setting
DPV Modulation Amplitude50mVOptimized DPV setting
Serum Recovery (Average)108.47%Standard addition method
Serum Precision (RSD%)1.09 (Intra-day), 2.36 (Inter-day)%Peak current repeatability

The electrochemical determination of Famciclovir utilized Cyclic Voltammetry (CV) for mechanistic studies and Differential Pulse Voltammetry (DPV) for quantification.

  1. Electrode Cleaning: The BDDE working electrode surface was mechanically cleaned using alumina powder and a polishing cloth prior to every measurement to ensure reproducibility.
  2. Electrochemical Setup: A standard three-electrode system was employed: BDDE (working), Ag/AgCl (3 M NaCl) (reference), and platinum wire (auxiliary).
  3. Buffer Optimization: Four supporting electrolytes (H2SO4, Britton-Robinson, Phosphate, and Acetate buffers) were tested across a pH range of 2.0-10.0. The pH 4.7 Acetate Buffer Solution (ABS) was selected for providing the highest peak current and best symmetry.
  4. Mechanistic Study (CV): CV scans (5-1000 mVs-1) confirmed an irreversible oxidation peak in the anodic direction, with no corresponding cathodic peak. The linear relationship between log Ip and log v (slope ≈ 0.48) confirmed the reaction was diffusion-controlled.
  5. Serum Sample Preparation (Protein Precipitation):
    • A mixture was prepared containing 1.0 mL FCV stock (1.0 x 10-2 M), 3.6 mL human serum, and 5.4 mL acetonitrile (for protein precipitation).
    • The mixture was sonicated for 15 minutes and centrifuged at 5000 rpm for 20 minutes to remove protein residue.
    • The resulting supernatant was diluted in the optimal buffer (pH 4.7 ABS) for DPV analysis.
  6. Quantification (DPV): Calibration plots were generated by measuring the anodic peak current against varying FCV concentrations in both standard solution and spiked serum.

The use of BDDE in this analytical context highlights its utility in several high-demand engineering and clinical fields, particularly where robust, sensitive, and rapid analysis is required.

  • Therapeutic Drug Monitoring (TDM): Provides a fast, point-of-care compatible method for monitoring antiviral drug (Famciclovir, Acyclovir analogs) concentrations in patient serum, crucial for optimizing dosing and minimizing toxicity.
  • Pharmaceutical Quality Control (QC): Enables rapid, high-sensitivity analysis of Active Pharmaceutical Ingredients (APIs) in raw materials and finished dosage forms, offering a low-cost alternative to complex chromatography.
  • Clinical Diagnostics and Bioanalysis: BDDE’s stability in complex biological matrices (like serum) makes it ideal for developing robust sensors for various biomarkers and drug metabolites.
  • Green Analytical Chemistry: The method reduces reliance on expensive, hazardous organic solvents and complex sample preparation (extraction, evaporation) associated with traditional HPLC/MS methods.
  • Advanced Electrochemical Sensing: Demonstrates the superior performance of unmodified BDDE surfaces compared to modified carbon electrodes, applicable to developing sensors for other nucleoside analogs and organic compounds.
View Original Abstract

The electrochemical oxidation of famciclovir was investigated in pH range 2.0-10.0 using differential pulse voltammetry at boron-doped diamond electrode. The experimental results from pH and scan rate studies showed that the oxidation behavior of famciclovir at boron doped diamond electrode was irreversible and diffusion-controlled. Also, by using differential pulse technique at electrode, the anodic peak current is obtained to be linear over the range of concentration 0.5 ”M - 12 ”M and 6 ”M - 100 ”M in pH 4.7 acetate buffer solution (ABS) for standard drug solution and human serum, respectively. Limits of detection were 0.022 ”M and 0.42 ”M for standard drug solution and human serum, respectively. The repeatability, reproducibility, selectivity, precision and accuracy of developed method in all media were investigated and calculated. This method was successfully applied for the analysis of famciclovir human serum samples.