DETERMINATION OF ANTI-CANCER DRUG PALBOCICLIB FROM HUMAN BIOLOGICAL FLUIDS BY USING DIFFERENTIAL PULSE VOLTAMMETRIC METHOD AT BORON DOPED DIAMOND ELECTRODE
At a Glance
Section titled âAt a Glanceâ| Metadata | Details |
|---|---|
| Publication Date | 2024-08-11 |
| Journal | Ankara Universitesi Eczacilik Fakultesi Dergisi |
| Authors | Melike Akan, ĂiÄdem KanbeĆ Dindar, Nazife Aslan, Bengi Uslu |
| Institutions | Ankara University, Ankara Hacı Bayram Veli University |
| Analysis | Full AI Review Included |
Executive Summary
Section titled âExecutive SummaryâThis study presents a highly sensitive and efficient electrochemical method for quantifying the anti-cancer drug Palbociclib in human biological fluids using a Boron-Doped Diamond Electrode (BDDE).
- Core Achievement: Development of a Differential Pulse Voltammetry (DPV) method utilizing BDDE for the direct analysis of Palbociclib in human serum and urine samples.
- Electrode Performance: The BDDE demonstrated superior chemical stability, enabling optimal operation in strongly acidic media (pH 2.0 Phosphate Buffer Solution).
- Reaction Kinetics: The oxidation behavior of Palbociclib was determined to be irreversible and regulated primarily by diffusion control (log Ip vs log v slope of 0.59, closely approximating the theoretical 0.5).
- High Sensitivity: The method achieved excellent limits of detection (LOD), notably 1.31 nM in urine samples and 2.93 nM in human serum samples.
- Analytical Range: Linear concentration ranges were established from 0.01-1 ”M for standard solutions and 0.02-0.8 ”M for biological fluids.
- Method Advantages: The proposed technique is simple, inexpensive, and environmentally friendly, eliminating the time-consuming preconcentration, extraction, and separation steps required by conventional chromatographic methods (e.g., LC-MS/MS).
- Validation: High accuracy was confirmed through recovery studies in spiked serum (98.75%) and urine (99.75%) samples.
Technical Specifications
Section titled âTechnical Specificationsâ| Parameter | Value | Unit | Context |
|---|---|---|---|
| Working Electrode Material | Boron-Doped Diamond (BDDE) | N/A | 3 mm diameter |
| Optimal Supporting Electrolyte | pH 2.0 | N/A | Phosphate Buffer Solution (PBS) |
| Reaction Mechanism | Irreversible | N/A | Diffusion-controlled process |
| Diffusion Control Slope (log Ip vs log v) | 0.59 | N/A | Experimental value (Theoretical for diffusion: 0.5) |
| Anodic Potential (Standard) | 756 | mV | Measured via DPV |
| Anodic Potential (Serum/Urine) | 786 | mV | Measured via DPV |
| Standard Linearity Range | 0.01-1 | ”M | Standard drug solution |
| Biological Fluid Linearity Range | 0.02-0.8 | ”M | Human serum and urine |
| Limit of Detection (LOD) | 1.31 | nM | Urine sample (most sensitive matrix) |
| Limit of Detection (LOD) | 2.93 | nM | Human serum sample |
| Serum Recovery (Average) | 98.75 | % | Accuracy study (n=5) |
| Urine Recovery (Average) | 99.75 | % | Accuracy study (n=5) |
| DPV Modulation Amplitude | 50 | mV | Electrochemical setup parameter |
| DPV Interval Time | 500 | ms | Electrochemical setup parameter |
| DPV Step Potential | 10 | mV | Electrochemical setup parameter |
Key Methodologies
Section titled âKey MethodologiesâThe electrochemical analysis utilized a standard three-electrode cell setup with specific sample preparation protocols for complex biological matrices.
- Electrode System:
- Working Electrode: Boron-Doped Diamond Electrode (BDDE).
- Reference Electrode: Ag/AgCl (3 M NaCl).
- Counter Electrode: Platinum wire.
- Electrode Pretreatment: Prior to each measurement, the BDDE surface was mechanically prepared using alumina powder followed by polishing cloth.
- Electrochemical Techniques: Cyclic Voltammetry (CV) was used for mechanistic studies (scan rate variation, pH effects), and Differential Pulse Voltammetry (DPV) was used for quantification.
- Optimal Condition Selection: CV studies across various media (H2SO4, BRT, PBS) and pH ranges (2.0-9.0) identified pH 2.0 PBS as the optimal supporting electrolyte due to superior peak symmetry and current reproducibility.
- Serum Sample Preparation (Protein Precipitation):
- Serum samples were spiked with Palbociclib stock solution.
- Proteins were precipitated using acetonitrile (5.4 ml acetonitrile added to 3.6 ml serum/drug mixture).
- The mixture was sonicated for 15 minutes and centrifuged at 5000 rpm for 20 minutes to isolate the supernatant for analysis.
- Urine Sample Preparation:
- Spiked urine samples were treated with acetonitrile (0.7 ml) as a precipitating agent.
- The mixture was vortexed for 10 minutes and centrifuged at 5000 x g for 5 minutes to remove residues before voltammetric analysis.
Commercial Applications
Section titled âCommercial ApplicationsâThe development of a robust, sensitive electrochemical sensor based on BDDE technology has direct implications for several high-value engineering and clinical sectors.
- Therapeutic Drug Monitoring (TDM): Enables rapid, accurate, and cost-effective monitoring of Palbociclib levels in patient biofluids, crucial for optimizing chemotherapy dosage and minimizing adverse effects.
- Clinical Point-of-Care (POC) Diagnostics: BDDE sensors facilitate the creation of portable, simple analytical devices for clinical settings, reducing reliance on centralized, expensive laboratory equipment (e.g., LC-MS/MS).
- Pharmaceutical Analysis and Quality Control: BDDEâs wide potential window and chemical inertness make it ideal for analyzing electroactive drug compounds and impurities in pharmaceutical formulations under harsh chemical conditions.
- Bioanalytical Sensor Development: The demonstrated success in complex matrices (serum, urine) validates BDDE as a platform for developing highly selective sensors for other electroactive biomarkers and drug metabolites.
- High-Stability Electrochemical Systems: BDDE materials are critical for applications requiring long-term stability and resistance to fouling or aggressive chemical environments, such as industrial wastewater treatment or complex chemical synthesis monitoring.
View Original Abstract
Objective: A very efficient and sensitive electrochemical technique utilizing differential pulse voltammetry (DPV) at a boron-doped diamond electrode (BDDE) was devised to measure Palbociclib in this study. Material and Method: All experiments employed typical three-electrode cell of 10 ml capacity in conjunction with boron-doped diamond electrode, a platinum wire counter electrode, and an Ag/AgCl reference electrode. During electrochemical measurements, DPV and cyclic voltammetry (CV) methods was utilized at BDDE. Result and Discussion: Based on experimental findings from electrochemical characterization investigations, it was determined that oxidation behavior of Palbociclib in BDDE is irreversible and regulated by diffusion. Anodic peak current exhibited a linear relationship within concentration range of 0.01-1 ”M, 0.02-0.8 ”M, and 0.02-0.8 ”M in pH 2.0 phosphate buffer solution (PBS) for reference substance solution, human serum, and urine samples, respectively. Limits of detection were found as 2.28 nM, 2.93 nM, and 1.31 nM for standard drug solution, human serum and urine samples, respectively. In order to validate the developed method, its repeatability, reproducibility, selectivity, precision and accuracy in all environments were investigated and calculated. This method was successfully applied for the analysis of Palbociclib in human serum and urine samples .