Sensitive Voltammetric Detection of Chloroquine Drug by Applying a Boron-Doped Diamond Electrode

At a Glance

Metadata	Details
Publication Date	2020-11-11
Journal	C – Journal of Carbon Research
Authors	Geiser Gabriel Oliveira, Déborah C. Azzi, Tiago Almeida Silva, Paulo Roberto de Oliveira, Orlando Fatibello‐Filho
Institutions	Universidade Federal de São Carlos, Federal Center for Technological Education of Minas Gerais
Citations	19
Analysis	Full AI Review Included

Executive Summary

This research details the development of a highly sensitive electroanalytical method for detecting the antimalarial drug chloroquine using a Boron-Doped Diamond (BDD) electrode.

Core Achievement: The method achieved a record-low Limit of Detection (LOD) of 2.0 nmol L^-1 for chloroquine, which is approximately 10 times lower than the best LOD previously reported for this analyte using modified electrodes.
Optimal Sensor Configuration: Superior analytical performance was obtained using a Cathodically Pretreated BDD (CPT-BDD) electrode, which features a predominantly hydrogen-terminated surface.
Methodology: Square-Wave Voltammetry (SWV) was employed, leveraging the BDD’s stability and wide potential window to measure the irreversible anodic oxidation of chloroquine.
Analytical Range: The method demonstrated linearity in the submicromolar range (0.01 to 0.25 µmol L^-1), suitable for trace analysis.
Efficiency and Robustness: The procedure is direct, requiring no preconcentration step, and utilizes the inherent robustness and fast charge-transfer kinetics (kº = 0.0056 cm s^-1) of the BDD material.
Material Quality: The BDD film, synthesized via Hot Filament Chemical Vapour Deposition (HFCVD) with 8000 ppm Boron, exhibited a uniform pyramidal structure, confirming high electrochemical quality.

Technical Specifications

Parameter	Value	Unit	Context
BDD Synthesis Method	HFCVD	N/A	Hot Filament Chemical Vapour Deposition.
BDD Doping Level	8000	ppm	Boron content in the film.
Working Electrode Exposed Area	0.32	cm²	Area fixed on conductive copper support.
Cathodic Pretreatment Current Density	-0.5	A cm^-2	Applied for 180 s (Hydrogen termination).
Anodic Pretreatment Current Density	+0.5	A cm^-2	Applied for 30 s (Oxygen termination).
Calculated Electroactive Area	0.285	cm²	Determined via Randles-Sevick equation.
Heterogeneous Electron Transfer Rate (kº)	0.0056	cm s^-1	Calculated for the Fe(CN)₆^3-/4- redox probe.
Limit of Detection (LOD)	2.0	nmol L^-1	Achieved using CPT-BDD and SWV.
Analytical Sensitivity	12.2	µA L µmol^-1	Slope of the linear analytical curve.
Linear Concentration Range	0.01 to 0.25	µmol L^-1	Submicromolar detection range.
Repeatability (RSD)	4.2	%	Relative Standard Deviation (n=3).
Optimal Supporting Electrolyte pH	6.0	N/A	0.1 mol L^-1 Britton-Robson buffer.
Optimal SWV Frequency (f)	100	Hz	Optimized Square-Wave Voltammetry parameter.

Key Methodologies

The sensitive detection relies on optimizing the BDD surface termination and the Square-Wave Voltammetry (SWV) parameters.

BDD Film Preparation:
- BDD films were synthesized on p-silicon wafers using the Hot Filament Chemical Vapour Deposition (HFCVD) technique.
- The film exhibited a uniform pyramidal structure, characteristic of preferential textured growth along the (111) planes.
Electrochemical Pretreatment (Surface Termination):
- The BDD electrode was subjected to two distinct pretreatments in 0.50 mol L^-1 H₂SO₄ to control surface termination:
  - Cathodic Pretreatment (CPT-BDD): Applied -0.5 A cm^-2 for 180 s, resulting in a predominantly hydrogen-terminated surface. This configuration yielded the best-defined anodic peak and highest current intensity for chloroquine.
  - Anodic Pretreatment (APT-BDD): Applied +0.5 A cm^-2 for 30 s, resulting in an oxygen-terminated surface.
- CPT-BDD was selected for all subsequent analytical studies due to its enhanced voltammetric response.
Electrochemical Characterization:
- Cyclic Voltammetry (CV) using 1.0 x 10^-3 mol L^-1 K₃Fe(CN)₆ confirmed the BDD’s high quality: a peak-to-peak separation (ΔE_p) of 83 mV (close to the theoretical 59.2 mV) and a current ratio (I_pa/I_pc) of 1.04, indicating near-reversible, diffusion-controlled electron transfer.
Chloroquine Detection (SWV Optimization):
- The electrochemical activity of chloroquine was confirmed as an irreversible anodic oxidation reaction, related to the aminoquinoline moiety.
- Optimal analytical conditions were established using 0.1 mol L^-1 Britton-Robson buffer (pH 6.0).
- Optimized SWV parameters were set at a frequency of 100 Hz, amplitude of 50 mV, and potential increment of 5 mV to maximize the anodic peak signal.

Commercial Applications

The use of robust, high-performance BDD electrodes combined with pulsed voltammetry is critical for applications requiring trace analysis and high throughput.

Industry/Sector	Relevance of BDD Technology
Pharmaceutical Manufacturing & QC	Provides a fast, sensitive, and reliable method for the quantitative control of active pharmaceutical ingredients (APIs) like chloroquine in raw materials and final formulations.
Clinical and Medical Monitoring	Enables the detection of nanomolar drug concentrations in biological fluids (e.g., plasma or urine), essential for therapeutic drug monitoring (TDM) where the margin between therapeutic and toxic doses is narrow.
Electroanalytical Sensor Development	BDD serves as a superior platform for developing next-generation electrochemical sensors due to its low background current, chemical inertness, and resistance to fouling.
Flow Injection Analysis (FIA) Systems	BDD’s robustness and stability are paramount for integration into high-frequency analytical methods, such as FIA coupled with multiple pulse amperometric detection, enabling rapid simultaneous determination of multiple analytes.
Environmental Trace Analysis	The material’s resistance to adsorption and fouling makes it highly effective for detecting trace organic contaminants, pesticides, and drug residues in complex environmental water samples.

View Original Abstract

In this research, a boron-doped diamond (BDD) electrode has been explored to detect the chloroquine drug. The electrochemical performance of BDD electrode towards the irreversible anodic response of chloroquine was investigated by subjecting this electrode to the cathodic (−0.5 A cm−2 by 180 s, generating a predominantly hydrogen-terminated surface) and anodic (+0.5 A cm−2 by 30 s, oxygen-terminated surface) pretreatments. The cathodically pretreated BDD electrode ensured a better-defined anodic peak and higher current intensity. Thus, by applying the cathodically pretreated BDD electrode and square-wave voltammetry (SWV), the analytical curve was linear from 0.01 to 0.25 µmol L−1 (correlation coefficient of 0.994), with sensitivity and limit of detection of 12.2 µA L µmol−1 and 2.0 nmol−1, respectively. This nanomolar limit of detection is the lowest recorded so far with modified and unmodified electrodes.

Tech Support

Original Source

DOI: https://doi.org/10.3390/c6040075

References

2020 - Mechanisms of action of hydroxychloroquine and chloroquine: Implications for rheumatology [Crossref]
2015 - Chloroquine analogues in drug discovery: New directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases [Crossref]
2017 - Increased incidence of gastrointestinal side effects in patients taking hydroxychloroquine: A brand-related issue? [Crossref]
2016 - Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision) [Crossref]
2020 - Of chloroquine and COVID-19 [Crossref]
2020 - A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 [Crossref]
2019 - Disposable and flexible electrochemical sensor made by recyclable material and low cost conductive ink [Crossref]
2011 - Factorial design and response surface: Voltammetric method optimization for the determination of ag(i) employing a carbon nanotubes paste electrode