Determination of 4-aminophenol in a pharmaceutical formulation using surface enhanced Raman scattering: from...

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Pharmaceutical Analysis

Background:

• Quantification of impurities like 4-aminophenol in pharmaceutical formulations is crucial for drug safety and quality control.
• Traditional analytical methods may lack sensitivity or require complex sample preparation for detecting low-level impurities.
• Surface-enhanced Raman scattering (SERS) offers high sensitivity and specificity for molecular detection.

Purpose of the Study:

• To develop and validate a SERS method for quantifying 4-aminophenol in acetaminophen (paracetamol) pharmaceutical formulations.
• To optimize SERS sample preparation for enhanced Raman signal.
• To establish a robust and reliable analytical method for impurity profiling in pharmaceuticals.

Main Methods:

• Synthesis of silver nanoparticles using the Lee-Meisel method as the SERS substrate.
• Characterization of silver nanoparticles' size and zeta potential to ensure reproducibility.
• Design of experiments to optimize SERS sample preparation (nanoparticle and aggregating agent concentrations).
• Validation of the SERS method using tolerance intervals and accuracy profiles from 3 to 15 µg mL⁻¹.
• Standard addition method for calibration with spiked pharmaceutical formulation samples.

Main Results:

• A repeatable synthesis of silver nanoparticles was achieved, confirmed by size and zeta potential analysis.
• Optimized SERS sample preparation maximized Raman signal enhancement.
• The developed SERS method was successfully validated for quantifying 4-aminophenol, demonstrating accuracy and precision.
• The method proved reliable despite inherent SERS stability challenges, validated across multiple operators and nanoparticle batches.

Conclusions:

• The developed SERS method provides a validated, sensitive, and specific approach for quantifying 4-aminophenol in acetaminophen formulations.
• This study demonstrates the successful application of SERS in pharmaceutical quality control, overcoming previous limitations.
• The validated SERS method offers a valuable tool for impurity analysis in the pharmaceutical industry.