Gemcitabine Direct Electrochemical Detection from Pharmaceutical Formulations Using a Boron-Doped Diamond Electrode

At a Glance

Metadata	Details
Publication Date	2021-09-10
Journal	Pharmaceuticals
Authors	Iulia Rus, Alexandra Pusta, Mihaela Tertiş, Cristina Barbălată, Ioan Tomuță
Institutions	Iuliu Hațieganu University of Medicine and Pharmacy
Citations	15
Analysis	Full AI Review Included

Technical Documentation & Analysis: Boron-Doped Diamond for Gemcitabine Detection

Executive Summary

This research successfully demonstrates a simple, fast, and highly robust electrochemical method for the direct detection of the anticancer drug Gemcitabine (GMB) using a Boron-Doped Diamond Electrode (BDDE).

Core Value Proposition: The BDDE enables direct, surfactant-free GMB detection, overcoming stability and complexity issues associated with traditional modified electrodes (e.g., MIPs, DNA-modified surfaces) or noble metal electrodes.
Material Advantage: The BDDE’s wide electrochemical potential window (tested up to 2.5 V) and inherent stability were critical for observing the GMB oxidation peak (~2.2 V vs. Ag/AgCl), which was undetectable on conventional electrodes (GCE, SPEs, Gold).
Optimized Methods: Two strategies were optimized: Differential Pulse Voltammetry (DPV) for rapid analysis and Amperometry (AMP) for superior sensitivity.
High Sensitivity: Amperometry achieved a low limit of detection (LOD) of 0.15 µg/mL (Linear Range: 0.5-65 µg/mL), making it suitable for trace analysis in pharmaceutical quality control and drug release studies.
Physiological Relevance: The methods were optimized for Phosphate-Buffered Saline (PBS) at physiological pH 7.4 and tumor media pH 5.5, demonstrating immediate applicability in clinical and research settings.
Robustness: Statistical analysis (ANOVA, Bland-Altman plot) confirmed excellent correlation and interchangeability with established control methods (HPLC-UV and UV-Vis spectrophotometry).

Technical Specifications

The following hard data points were extracted from the optimized electrochemical detection strategies utilizing the Boron-Doped Diamond Electrode (BDDE).

Parameter	Value	Unit	Context
Electrode Material	Boron-Doped Diamond (BDDE)	N/A	Used for high stability and wide potential window
GMB Oxidation Peak Potential	~2.2	V	Anodic peak observed in DPV (vs. Ag/AgCl)
Electrochemical Process Control	Diffusion-controlled	N/A	Confirmed by scan rate studies
Optimized DPV Scan Rate	100	mV/s	Chosen for analysis
DPV Linear Range (pH 7.4)	2.5-50	µg/mL	Phosphate-Buffered Saline (PBS)
DPV Limit of Detection (LOD)	0.85	µg/mL	Calculated based on S/N = 3
Amperometry Applied Potential	1.9	V	Optimized for current leap detection
Amperometry Linear Range	0.5-65	µg/mL	Highly sensitive method (pH 7.4 or 5.5)
Amperometry Limit of Detection (LOD)	0.15	µg/mL	Calculated based on S/N = 3
Optimized Electrolyte pH	7.4 and 5.5	N/A	Physiological (7.4) and tumor media (5.5) relevance

Key Methodologies

The following steps outline the critical parameters and procedures used to achieve optimized GMB detection on the BDDE:

Electrode Preparation: The 3-mm diameter BDDE was mechanically polished using 3-µm diamond polish, followed by 30 minutes of sonication in ultrapure water to ensure a clean, active surface.
Electrochemical Setup: A conventional three-electrode cell was employed, utilizing the BDDE as the working electrode, a solid Ag/AgCl reference electrode, and a platinum wire counter-electrode.
Buffer Optimization: The oxidation signal intensity was tested across a wide range of pH values (pH 2-12) using Britton Robinson Buffer (BRB). The highest intensity was observed at pH 5.
Electrolyte Selection: Phosphate-Buffered Saline (PBS) at pH 7.4 (0.05 M) was selected for primary analysis due to its physiological relevance, with additional studies performed at pH 5.5.
Voltammetry Parameters (DPV): The optimized DPV recipe included a step potential of 0.01 V, modulation amplitude of 0.05 V, modulation time of 0.02 s, interval time of 0.1 s, and a scan rate of 100 mV/s.
Amperometry Parameters (AMP): The procedure was conducted at a fixed potential of 1.9 V, monitoring the current response upon successive, small-volume additions of concentrated GMB solution under continuous stirring.
Validation: The electrochemical results were rigorously compared against established analytical standards: HPLC-UV (mobile phase: 0.1% H₃PO₄-methanol 97:3, v/v; detection at 272 nm) and UV-Vis Spectrophotometry (λ_max = 270 nm).

6CCVD Solutions & Capabilities

The successful implementation of the BDDE for high-performance electrochemical sensing of Gemcitabine highlights the critical need for high-quality, application-specific Boron-Doped Diamond materials. 6CCVD is uniquely positioned to supply and enhance the materials required for this research and its commercial scaling.

Applicable Materials

To replicate or extend this research into commercial sensor development or high-throughput quality control, 6CCVD recommends the following materials:

Heavy Boron-Doped Polycrystalline Diamond (PCD BDD): This material provides the necessary wide potential window, chemical inertness, and stability demonstrated in the paper. 6CCVD offers PCD BDD wafers up to 125mm in diameter and thicknesses from 0.1 µm to 500 µm, ideal for mass production of sensor arrays.
Single Crystal Diamond (SCD BDD): For ultra-high precision or fundamental research requiring maximum material purity and crystalline perfection, 6CCVD can supply SCD BDD plates up to 10x10 mm.

Customization Potential

The study utilized a specific 3-mm diameter BDDE disc. 6CCVD’s advanced fabrication capabilities ensure researchers and engineers can acquire materials tailored precisely to their sensor design requirements:

Research Requirement	6CCVD Customization Capability	Technical Advantage
Custom Dimensions	Plates/wafers up to 125mm (PCD) or custom laser-cut discs (e.g., 3-mm diameter)	Ensures precise fit for existing electrochemical cell designs and scalable manufacturing.
Surface Finish	Polishing to Ra < 5nm (Inch-size PCD) or Ra < 1nm (SCD)	Provides a superior starting surface, minimizing the need for extensive 3-µm mechanical polishing and improving sensor reproducibility and baseline stability.
Metalization	Internal capability for Au, Pt, Pd, Ti, W, Cu contacts	Allows for the deposition of custom contact pads or interconnects (e.g., Ti/Pt/Au stack) directly onto the BDD surface, ensuring robust electrical connection for sensor integration.
Thickness Control	SCD/PCD layers from 0.1 µm up to 500 µm	Enables optimization of the BDD layer thickness based on specific conductivity and application needs (e.g., thin films for microelectrode arrays).

Engineering Support

The development of fast, robust electrochemical assays for pharmaceutical quality control and drug release monitoring (as demonstrated by the optimization for physiological pH 7.4 and tumor pH 5.5) is a critical application area. 6CCVD’s in-house PhD team specializes in CVD diamond material science and electrochemical applications. We provide expert consultation on:

Optimizing boron doping levels for specific electrochemical sensitivity and conductivity requirements.
Selecting the optimal diamond grade (SCD vs. PCD) based on required surface area and cost constraints.
Designing custom metalization schemes for seamless integration into microfluidic or sensor platforms.

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

View Original Abstract

The development of fast and easy-to-use methods for gemcitabine detection is of great interest for pharmaceutical formulation control in both research laboratories and hospitals. In this study, we report a simple, fast and direct electrochemical method for gemcitabine detection using a boron-doped diamond electrode. The electrochemical oxidation of gemcitabine on a boron-doped diamond electrode was found to be irreversible in differential pulse voltammetry, and scan rate influence studies demonstrated that the process is diffusion-controlled. The influence of the pH and supporting electrolytes were also tested, and the optimized differential pulse voltammetry method was linear in the range of 2.5-50 μg/mL, with a detection limit of 0.85 μg/mL in phosphate-buffered saline (pH 7.4; 0.1 M). An amperometric method was also optimized for gemcitabine detection. The linear range of the method was 0.5-65 μg/mL in phosphate-buffered saline of pH 7.4 as well as pH 5.5, the limit of detection being 0.15 μg/mL. The optimized differential pulse voltammetry and amperometric detection strategies were successfully applied to pharmaceutical formulations, and the results were compared to those obtained by high-performance liquid chromatography and UV-Vis spectrophotometry with good correlations.

Tech Support

Original Source

DOI: https://doi.org/10.3390/ph14090912

References

2014 - Summary: Gemcitabine Pathway [Crossref]
2005 - Role of Gemcitabine in Cancer Therapy [Crossref]
1997 - Gemcitabine. A Review of Its Pharmacology and Clinical Potential in Non-Small Cell Lung Cancer and Pancreatic Cancer [Crossref]
2016 - Pharmacokinetics and Pharmacogenetics of Gemcitabine as a Mainstay in Adult and Pediatric Oncology: An EORTC-PAMM Perspective [Crossref]
2019 - Development of Liposomal Gemcitabine with High Drug Loading Capacity [Crossref]
2019 - Tumor-Specific Delivery of Gemcitabine with Activatable Liposomes [Crossref]
2017 - Effective Targeting of Gemcitabine to Pancreatic Cancer through PEG-Cored Flt-1 Antibody-Conjugated Dendrimers [Crossref]
2015 - Controlled Delivery of Gemcitabine Hydrochloride Using Mannosylated Poly(Propyleneimine) Dendrimers [Crossref]
2020 - Cytotoxic Effects of Gemcitabine-Loaded Solid Lipid Nanoparticles in Pancreatic Cancer Cells [Crossref]
2015 - Stability-Indicating HPLC Determination of Gemcitabine in Pharmaceutical Formulations [Crossref]