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Voltammetric determination of antipsychotic drug flupentixol HCl in human serum at a boron-doped diamond electrode

MetadataDetails
Publication Date2022-05-31
JournalJournal of the Turkish Chemical Society Section A Chemistry
AuthorsBurcin Bozal‐Palabiyik
InstitutionsAnkara University
AnalysisFull AI Review Included

Technical Documentation & Analysis: Voltammetric Determination of Flupentixol HCl using Boron-Doped Diamond Electrodes

Section titled “Technical Documentation & Analysis: Voltammetric Determination of Flupentixol HCl using Boron-Doped Diamond Electrodes”

This research validates the superior performance of Boron-Doped Diamond Electrodes (BDDE) for highly sensitive bioanalytical sensing, specifically for Therapeutic Drug Monitoring (TDM) of the antipsychotic drug Flupentixol (FLP) in human serum.

  • Core Achievement: Successful development of a simple, fast, and accurate Differential Pulse Voltammetry (DPV) method for FLP determination in synthetic human serum.
  • Material Validation: BDDE demonstrated exceptional robustness, chemical inertness, and resistance to electrode fouling, outperforming traditional carbon-based electrodes (e.g., Glassy Carbon Electrode, GCE).
  • High Sensitivity: Achieved a low Limit of Detection (LOD) of 1.08 x 10-7 M in serum, comparable to or better than complex, high-cost chromatographic methods (e.g., HPLC).
  • Diffusion Control: The oxidation behavior of FLP at the BDDE surface was confirmed to be irreversible and diffusion-controlled, indicating stable mass transport kinetics.
  • Bioanalytical Accuracy: High average recovery (99.91%) from spiked serum samples confirms the method’s accuracy and precision for clinical TDM applications.
  • 6CCVD Value Proposition: This study reinforces the critical need for high-quality, heavily doped BDD materials, which 6CCVD supplies in custom dimensions and specifications for advanced electrochemical sensing platforms.

The following hard data points were extracted from the voltammetric determination study using the Boron-Doped Diamond Electrode (BDDE).

ParameterValueUnitContext
Working Electrode MaterialBoron-Doped Diamond (BDD)N/ADemonstrates metal-like conductivity (103 - 104 ppm doping)
Working Electrode Diameter3mmStandard commercial size used in the study
Optimum Supporting ElectrolytepH 2.0N/ABritton-Robinson (BR) Buffer solution
Measured Potential (Ep)986mVvs Ag/AgCl reference electrode
Bulk Linear Range6.0 x 10-7 to 8.0 x 10-6MConcentration range for bulk FLP solution
Serum Linear Range8.0 x 10-7 to 1.0 x 10-5MConcentration range for spiked serum samples
Serum Limit of Detection (LOD)1.08 x 10-7MHigh sensitivity achieved in complex biological matrix
Serum Limit of Quantification (LOQ)3.61 x 10-7MRequired for accurate TDM
Average Serum Recovery99.91%High accuracy confirmed (n=5 measurements)
Inter-day Precision (RSD)2.83%Relative Standard Deviation for serum analysis
Mass Transport MechanismDiffusion-ControlledN/AConfirmed by linear Randles-Sevcik plot (ip vs v1/2)

The electrochemical determination of Flupentixol (FLP) utilized Differential Pulse Voltammetry (DPV) on a BDD electrode.

  1. Electrode Setup: A conventional three-electrode cell was employed, consisting of a 3 mm diameter BDDE working electrode, an Ag/AgCl (3 M NaCl) reference electrode, and a Platinum wire auxiliary electrode.
  2. Electrode Pre-treatment: The BDDE surface was mechanically cleaned before each measurement using alumina powder and a polishing cloth to ensure optimal surface activity and minimize fouling.
  3. Electrolyte Preparation: The measurement solution consisted of 20% methanol and pH 2.0 Britton-Robinson (BR) buffer solution (0.04 M), selected for providing the highest peak current and best peak shape.
  4. Voltammetric Technique Selection: Differential Pulse Voltammetry (DPV) was chosen as the primary working method due to its superior repeatability and sensitivity compared to Cyclic Voltammetry (CV) and Square Wave Voltammetry (SWV).
  5. Optimized DPV Parameters:
    • Step Potential: 10 mV
    • Modulation Amplitude: 50 mV
    • Modulation Time: 50 ms
    • Interval Time: 500 ms
  6. Sample Preparation: Serum proteins were precipitated using methanol and acetonitrile, followed by ultrasonication and centrifugation (5000 rpm for 15 minutes) to isolate the supernatant for analysis.

This research highlights the indispensable role of high-quality Boron-Doped Diamond (BDD) in developing next-generation bioanalytical sensors. 6CCVD is uniquely positioned to supply the materials required to replicate, scale, and advance this research into commercial TDM platforms.

To achieve the metal-like conductivity and robustness demonstrated in this study, researchers require heavily doped BDD material.

6CCVD Material SolutionSpecification & Relevance to Research
Heavy Boron-Doped Diamond (BDD)Required for metal-like conductivity (103 - 104 ppm B doping). 6CCVD provides BDD wafers optimized for low resistivity and wide potential windows, crucial for complex serum analysis.
Polycrystalline Diamond (PCD) WafersAvailable in large formats (up to 125 mm diameter) for high-throughput sensor array fabrication or integration into microfluidic devices.
Ultra-Smooth Polishing6CCVD offers polishing down to Ra < 5 nm for inch-size PCD/BDD. Minimizing surface roughness is critical for reducing the electrode fouling observed in the study (which caused peak intensity decrease).

The study utilized a small, 3 mm diameter electrode. 6CCVD specializes in providing custom geometries and integration features necessary for advanced electrochemical systems.

  • Custom Dimensions and Shapes: 6CCVD can supply BDD plates/wafers up to 125 mm in diameter and provide precision laser cutting services to create custom electrode geometries (e.g., 3 mm discs, microelectrode arrays, or integrated flow cell components).
  • Thickness Control: We offer precise BDD layer thickness control from 0.1 ”m up to 500 ”m, allowing optimization for specific electrochemical sensitivity and substrate integration.
  • Integrated Metalization: For seamless integration into sensor platforms, 6CCVD offers in-house metalization services, including Ti/Pt/Au contacts, which are essential for connecting the BDD working electrode to external circuitry.

The success of this voltammetric method relies heavily on selecting the correct diamond material properties (doping level, surface termination, and roughness).

  • Bioanalytical Expertise: 6CCVD’s in-house PhD engineering team specializes in material selection and optimization for electrochemical applications, including Therapeutic Drug Monitoring (TDM) and bioanalytical sensing.
  • Fouling Mitigation: We provide consultation on surface treatments and polishing specifications (Ra < 5 nm) to minimize electrode passivation and fouling, directly addressing the limitations noted in the research paper.
  • Global Supply Chain: 6CCVD ensures reliable, global shipping (DDU default, DDP available) of high-specification BDD materials, supporting international research and development efforts.

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

View Original Abstract

This study aims to offer a voltammetric method for determining the antipsychotic drug flupentixol from serum samples. According to pH and scan rate studies, the oxidation behavior of flupentixol at boron-doped diamond electrode was found as irreversible and diffusion-controlled. In order to determine flupentixol from bulk form and serum samples, differential pulse voltammetry was preferred as the working method because of the repeatability. Linear responses were obtained in the range of 6.0×10-7 - 8.0×10-6 M and 8.0×10-7 - 1.0×10-5 M for bulk form and serum samples in pH 2.0 Britton-Robinson buffer solution, with detection limit values of 1.09×10-7 M and 1.08×10-7 M, respectively. Required validation parameters were also studied and according to recovery from serum samples (99.91 %) and precision studies, it can be said that developed method was accurate and precise.