Flow injection analysis system with electrochemical detection for the simultaneous determination of nanomolar levels of acetaminophen and codeine

At a Glance

Metadata	Details
Publication Date	2017-04-26
Journal	Arabian Journal of Chemistry
Authors	Anderson M. Santos, Tiago Almeida Silva, Fernando Campanhã Vicentini, Orlando Fatibello‐Filho
Institutions	Universidade Federal de São Carlos
Citations	43
Analysis	Full AI Review Included

TECHNICAL DOCUMENTATION: BDD ELECTRODE FOR FIA-MPA NANOMOLAR DRUG DETECTION

6CCVD Ref: Electroanalytical Diamond for Flow Injection Analysis (FIA-MPA) Source Paper: Flow injection analysis system with electrochemical detection for the simultaneous determination of nanomolar levels of acetaminophen and codeine

Executive Summary

This research validates Boron-Doped Diamond (BDD) as the superior working electrode material for high-speed, highly sensitive electroanalytical determination of pharmaceuticals (Acetaminophen/Codeine) in complex matrices (biological fluids, commercial tablets).

Core Achievement: Simultaneous determination of Acetaminophen (ACP) and Codeine (COD) at nanomolar (nmol L^-1) concentrations using Flow Injection Analysis coupled with Multiple Pulse Amperometry (FIA-MPA).
Material Selection: Cathodically Pretreated Boron-Doped Diamond (CP-BDD) proved essential, providing enhanced anodic peak current and better separation between oxidation potentials compared to anodically pretreated diamond.
High Sensitivity: Achieved limits of detection (LODs) of 30 nmol L^-1 for ACP and 35 nmol L^-1 for COD—demonstrating suitability for trace level analysis.
High Speed: The optimized FIA-MPA system delivered an impressive analytical frequency of 90 samples per hour.
Robustness: BDD maintained stability and high performance in aggressive acidic media (0.05 mol L^-1 H₂SO₄) and complex biological fluid matrices (urine, human serum), demonstrating excellent recovery percentages (92.0-108%).
Replication Target: The success hinges on utilizing BDD with a high doping concentration (8000 ppm B/C) and precise surface pretreatment to achieve the necessary hydrogen-terminated surface characteristics.

Technical Specifications

Parameter	Value	Unit	Context
Electrode Material	Boron-Doped Diamond (BDD)	N/A	Used as working electrode
BDD Doping Level (B/C)	8000	ppm	Optimized heavy doping level
BDD Exposed Area	0.69	cm²	Electrode working surface area
Pretreatment Type	Cathodic (CP-BDD)	N/A	Hydrogen-terminated surface enhancement
Pretreatment Potential/Current	-0.04	A cm^-2	Applied current density
Pretreatment Duration	180	s	Time required for optimal surface condition
Supporting Electrolyte	0.05 mol L^-1 H₂SO₄	N/A	Optimized for signal intensity and BDD stability
Analytical Frequency	90	samples per hour	High-speed throughput via FIA
LOD (Acetaminophen, ACP)	30	nmol L^-1	Based on 3 times signal-to-noise ratio (3 S/N)
LOD (Codeine, COD)	35	nmol L^-1	Based on 3 S/N ratio
Linear Range (ACP)	80 nmol L^-1 to 100 µmol L^-1	N/A	Determined simultaneously
Linear Range (COD)	50 nmol L^-1 to 10 µmol L^-1	N/A	Determined simultaneously
MPA Pulse 1 (ACP Detection)	950	mV	Applied potential pulse (200 ms duration)
MPA Pulse 2 (COD Detection)	1400	mV	Applied potential pulse (100 ms duration)
Injected Sample Volume	350	µL	Optimized for minimal dilution effect
Flow Rate	3.8	mL min^-1	Optimized for mass transport/diffusion layer thinning

Key Methodologies

The study relies on precisely controlled MPCVD BDD material and optimized electrochemical recipes to achieve stability and sensitivity.

BDD Electrode Preparation:
- The BDD film (8000 ppm B/C) was fabricated (likely via MPCVD).
- The exposed working area was fixed at 0.69 cm².
BDD Cathodic Pretreatment (CP-BDD):
- Pretreatment solution: 0.5 mol L^-1 H₂SO₄.
- Cathodic current density applied: -0.04 A cm^-2.
- Duration: 180 s. (This step creates a stable, hydrogen-terminated surface critical for enhancing anodic current response.)
Flow Injection Analysis (FIA) Setup:
- Peristaltic pump maintained flow rate at 3.8 mL min^-1.
- Working electrolyte: 0.05 mol L^-1 H₂SO₄.
- Injection volume: 350 µL.
Multiple Pulse Amperometry (MPA) Application:
- The method utilized sequential, fixed potential pulses to allow for selective oxidation of the two analytes without cross-interference after signal subtraction.
- Pulse 1 (ACP Measurement): 950 mV for 200 ms. (Only ACP oxidizes).
- Pulse 2 (ACP + COD Measurement): 1400 mV for 100 ms. (Both compounds oxidize).
- COD concentration was derived using a Correction Factor (CF = 1.04 ± 0.02) and signal subtraction from the two potential pulses.

6CCVD Solutions & Capabilities

The high performance of the FIA-MPA system is directly attributable to the use of a high-quality, heavily Boron-Doped Diamond (BDD) electrode with a reproducible, electrochemically active surface. 6CCVD is uniquely positioned to supply the materials necessary to replicate, optimize, and scale this advanced electroanalytical technique.

Applicable Materials

To replicate or advance this research requiring extreme stability, a wide working window, and high conductivity, 6CCVD recommends:

Heavy Boron-Doped Diamond (BDD) Wafers: We offer custom doping levels, exceeding the 8000 ppm (B/C) required in the study. Our MPCVD BDD ensures exceptional purity, crystal quality, and homogeneity, critical for reliable electrochemical signal stability and low background current, especially in highly acidic environments (H₂SO₄).
Polycrystalline Diamond (PCD) Substrates: Available in wafers up to 125mm in diameter, these serve as ideal, stable platforms for the deposition of the BDD thin film.

Customization Potential

The experimental design specified a non-standard BDD exposed area of 0.69 cm² for integration into the flow-injection cell (wall-jet configuration).

Precision Fabrication: 6CCVD provides in-house precision laser cutting and machining services to achieve exact electrode dimensions and geometries (including discs, squares, and complex shapes) required for specific flow cell designs, ensuring perfect repeatability of the 0.69 cm² area.
Controlled Surface Quality: The success of the CP-BDD method relies on a high-quality, polished diamond surface. 6CCVD guarantees surface finishes with roughness down to Ra < 5nm for inch-size PCD, ensuring the reproducible formation of the hydrogen-terminated layer necessary for enhanced performance.
Metalization Capability: While not required for the working surface, 6CCVD offers internal metalization services (Au, Pt, Pd, Ti, W, Cu) for creating low-resistance ohmic contacts or integrating reference/auxiliary electrodes directly onto the diamond platform, simplifying electrochemical cell construction.

Engineering Support

This research highlights the continued relevance of diamond electrochemistry in pharmaceutical and biomedical sensing. 6CCVD’s in-house PhD material science team specializes in customizing diamond growth parameters (doping, orientation, surface termination) specifically for:

Electroanalytical Sensing: Assisting engineers with material selection and design consultation for next-generation systems targeting trace detection in complex biological matrices.
High-Throughput Methods: Optimizing BDD characteristics to maximize analytical frequency, stability, and corrosion resistance for industrial scale FIA-MPA systems.

Call to Action: For custom specifications or material consultation concerning BDD growth, precise electrode fabrication, or advanced electroanalytical projects similar to this nanomolar drug determination study, visit 6ccvd.com or contact our engineering team directly.

View Original Abstract

A simple, rapid and low-cost electroanalytical method is proposed for the determination of acetaminophen (ACP) and codeine (COD) at nanomolar levels in pharmaceutical and biological samples. The analytical procedure is based on a flow injection analysis system coupled to electrochemical detection, which was multiple pulse amperometry (FIA-MPA). Boron-doped diamond was used as the working electrode for electrochemical detection. The electrode was subjected to a cathodic pretreatment and was selected in this work due its good electrochemical performance. By applying the FIA-MPA method, after a number of optimization assays, the analgesics were simultaneously determined at excellent linear concentration ranges. The analytical curves ranged from 80 nmol L−1 to 100 µmol L−1 for ACP and from 50 nmol L−1 to 10 µmol L−1 for COD, and the obtained limits of detection were 30 nmol L−1 and 35 nmol L−1 for ACP and COD, respectively. The practical applicability of the electroanalytical method was evaluated from the ACP and COD determination in two sample matrices: commercial pharmaceutical samples and biological fluids. In the case of pharmaceutical formulation samples, the obtained results were statistically similar to those obtained using a reference chromatographic method. In addition, these drugs were simultaneously quantified in biological fluid samples of urine and human serum with excellent recovery percentages. Keywords: Paracetamol, Codeine, Flow injection analysis, Boron-doped diamond, Multiple pulse amperometry

Tech Support

Original Source

DOI: https://doi.org/10.1016/j.arabjc.2017.04.012

References

2014 - Facile simultaneous electrochemical determination of codeine and acetaminophen in pharmaceutical samples and biological fluids by graphene CoFe2O4 nanocomposite modified carbon paste electrode [Crossref]
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