Square-Wave Voltammetric Determination of Antihistaminic Drug Hydroxyzine in Pharmaceuticals Using a Boron-doped Diamond Electrode

At a Glance

Metadata	Details
Publication Date	2016-07-11
Journal	Orbital - The Electronic Journal of Chemistry
Authors	Jessica Scremin, Elen Romão Sartori
Institutions	Universidade Estadual de Londrina
Citations	3
Analysis	Full AI Review Included

Technical Documentation and Analysis: High-Performance BDD Electrodes for Pharmaceutical Voltammetry

6CCVD Analysis Reference: Orbital: The Electronic Journal of Chemistry, Vol 8 || No. 3 || April-June 2016. Title: Square-Wave Voltammetric Determination of Antihistaminic Drug Hydroxyzine in Pharmaceuticals Using a Boron-doped Diamond Electrode. Core Technology: Cathodically Pretreated Boron-Doped Diamond Electrode (BDDE)

Executive Summary

This research validates the use of highly doped, pretreated Boron-Doped Diamond Electrodes (BDDE) as a superior analytical platform for the precise and rapid determination of Hydroxyzine (HDZ), an antihistaminic drug, in commercial pharmaceutical formulations.

Core Achievement: Successful quantification of Hydroxyzine (HDZ) using Square-Wave Voltammetry (SWV) employing a cathodically pretreated BDDE.
Material Specification: The study utilized a high-concentration BDD film (8000 ppm Boron doping) on a Silicon (Si) substrate, crucial for achieving the wide working potential window required.
Performance Advantage: BDDE exhibited a significantly improved electrochemical response compared to traditional carbon electrodes, characterized by high sensitivity and superior repeatability.
Method Simplification: Unlike Glassy Carbon Electrode (GCE) methods, the BDDE approach requires no tedious sample pre-accumulation or surface regeneration (polishing) between measurements, enabling faster routine analysis.
Accuracy & Precision: Achieved excellent analytical results: a low detection limit of 0.43 µmol L^-1 and high intra-day precision (RSD 0.94%).
Manufacturing Insight: The enhanced activity and improved signal repeatability were directly linked to a specific cathodic pretreatment method, confirming the ability of 6CCVD materials to be readily engineered for optimized surface termination.
Validation: Results closely matched those obtained by the official, time-consuming potentiometric reference method (British Pharmacopoeia).

Technical Specifications

The following hard data points were extracted from the study detailing the electrode material properties and optimized analytical performance metrics.

Parameter	Value	Unit	Context
Electrode Material	Boron-Doped Diamond (BDD) Film on Si Wafer	N/A	Working Electrode (6CCVD specialty material)
Boron Dopant Concentration	8000	ppm	Heavy Doping required for metallic conductivity
Electrode Exposed Area	0.24	cm²	Custom dimensional requirement
Supporting Electrolyte	0.1 mol L^-1 HCl	N/A	Optimized medium (pH 1.0)
SWV Peak Potential (Eap)	1.25	V (vs. Ag/AgCl)	Anodic peak for HDZ oxidation
Linear Range (SWV)	0.50 to 20.0	µmol L^-1	Excellent linearity (r = 0.9989)
Detection Limit (LOD)	0.43	µmol L^-1	High sensitivity achievement
Transfer Electrons (n)	2	N/A	Calculated from Eap vs. log f plot
Intra-Day Repeatability (RSD)	0.94	%	Excellent precision over successive runs (n=10)
SWV Frequency (f)	70	s^-1	Optimized Square-Wave Voltammetry Parameter
Pulse Amplitude (a)	50	mV	Optimized Square-Wave Voltammetry Parameter
Scan Increment (ΔEs)	5	mV	Optimized Square-Wave Voltammetry Parameter

Key Methodologies

The following is a concise summary of the steps and parameters utilized to fabricate and operate the high-performance BDDE sensor system for HDZ quantification.

Electrode Preparation (Substrate & Doping): An 8000 ppm Boron-Doped Diamond film was deposited onto a Silicon (Si) wafer, manufactured by MPCVD.
Electrode Shaping: The working electrode surface was precisely defined to an exposed area of 0.24 cm².
Electrochemical Pretreatment (Anodic Step): The BDDE was first anodically pretreated in 0.5 mol L^-1 H₂SO₄ solution by applying a current of 0.5 A cm^-2 for 30 seconds.
Electrochemical Pretreatment (Critical Cathodic Step): The BDDE was then cathodically pretreated in 0.5 mol L^-1 H₂SO₄ solution by applying a current of -0.5 A cm^-2 for 120 seconds. (This step created a predominantly hydrogen-terminated surface, drastically increasing electrochemical activity and repeatability.)
Electrolyte Selection: Cyclic Voltammetry (CV) confirmed 0.1 mol L^-1 HCl solution (pH 1.0) provided the best-defined oxidation peak and was selected as the supporting electrolyte.
Analytical Optimization: Square-Wave Voltammetry (SWV) parameters were optimized (f=70 s^-1, a=50 mV, ΔEs=5 mV) to maximize the anodic peak current for HDZ oxidation (Eap = 1.25 V).
Quantification: Analytical curves were constructed via standard addition, and the HDZ concentration was determined by direct interpolation.

6CCVD Solutions & Capabilities

6CCVD is uniquely positioned to supply the next generation of advanced BDD materials required to replicate and extend this high-impact pharmaceutical research. Our expertise in custom MPCVD fabrication aligns perfectly with the stringent demands of electroanalytical engineering.

Applicable Materials

The successful operation of this sensor relies on a heavily doped diamond film to ensure metallic conductivity and a wide operational potential window.

Heavy Boron-Doped PCD/SCD: 6CCVD offers high-quality BDD films, optimized for electrochemical performance, with Boron doping levels well within the 1000 ppm to >10,000 ppm (1%) range.
- Recommendation: For direct replication, we recommend our Heavy Boron-Doped Polycrystalline Diamond (PCD) wafers on Si or custom substrates, ensuring the required 8000 ppm concentration for robust, high-current density applications.
Custom Thickness: We supply BDD films at the required thickness range for sensor integration, from 0.1 µm up to 500 µm, offering flexibility in impedance and stability optimization.

Customization Potential

The required working electrode area (0.24 cm²) and the use of a Si substrate are standard capabilities at 6CCVD.

Requirement from Paper	6CCVD Capability	Value Proposition
Custom Electrode Area (0.24 cm²)	Precision Laser Cutting: We cut wafers up to 125mm (PCD) to any required geometry or size, ensuring perfect integration into existing electrochemical cells.	Rapid prototyping and manufacturing of non-standard geometries.
Substrate Compatibility	Si, Quartz, Alumina: We fabricate BDD films directly on engineering-grade substrates, matching the Si substrate used in this research.	Seamless material replacement and process scalability.
Electrode Termination Control	In-House Surface Treatment Expertise: Our engineers advise on and perform specific surface preparation (Hydrogen, Oxygen, Fluorine termination) tailored for optimal sensitivity and pretreatment efficacy (e.g., maximizing the cathodic pretreatment response).	Guaranteed material consistency and analytical performance.
Metalization Integration (Future Extension)	Internal Metalization Services (Au, Pt, Ti, W): While this paper did not require metal contacts on the working area, 6CCVD provides custom metal pads and tracks for low-resistance contacts and chip integration (e.g., Ti/Pt/Au contact layers).	Full integration and packaging support for scaled device manufacturing.

Engineering Support

This research demonstrates the crucial role of the BDDE surface state (hydrogen termination via cathodic pretreatment) in maximizing the oxidation signal of complex organic molecules like HDZ.

6CCVD’s in-house PhD materials science and engineering team specializes in optimizing diamond material properties for electrochemical sensing. We offer dedicated consultation for projects related to:

Pharmaceutical Quality Control: Developing fast, sensitive, and reusable sensors for active pharmaceutical ingredient (API) analysis.
Voltammetric & Amperometric Sensing: Tuning BDD doping and surface termination to achieve target LODs and linear ranges in demanding acidic or alkaline media.
Electrochemical Device Scale-Up: Assisting clients in transitioning lab-scale BDDE prototypes to manufacturable wafers and plates up to 125 mm diameter.

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

View Original Abstract

The determination of antihistaminic hydroxyzine using square-wave voltammetry and a cathodically pretreated boron-doped diamond electrode is described. The obtained analytical curve was linear in the hydroxyzine concentration range 0.50 - 20.0 mmol L-1 in 0.1 mol L-1 HCl solution, with a detection limit of 0.43 mmol L-1. Addition and recovery studies in commercial tables and liquid formulations showed excellent recovery values ranging from 94.3 % to 104 %. Furthermore, the proposed method was successfully applied in the determination of hydroxyzine in several pharmaceutical formulations and the results were in a close agreement at a 95 % confidence level with those obtained using an official potentiometric method. DOI: <a href=“http://dx.doi.org/10.17807/orbital.v8i3.833”>http://dx.doi.org/10.17807/orbital.v8i3.833</a>

Tech Support

Original Source

DOI: https://doi.org/10.17807/orbital.v8i3.833