Acetaminophen determination in low-dose pharmaceutical syrup by NIR spectroscopy

Area of Science:

• Pharmaceutical Technology
• Analytical Chemistry
• Spectroscopy

Background:

• Accurate quantification of active pharmaceutical ingredients (APIs) is crucial for drug product quality.
• Near-infrared (NIR) spectroscopy offers a rapid, non-invasive analytical technique for pharmaceutical analysis.
• Developing robust calibration models is essential for reliable spectroscopic measurements in complex formulations.

Purpose of the Study:

• To develop and validate a robust near-infrared (NIR) calibration model for determining acetaminophen content in a low-dose syrup formulation (2%, w/v).
• To assess the model's accuracy and reliability across a defined range of acetaminophen concentrations and various sources of variability.
• To evaluate the potential of the NIR model for real-time monitoring of acetaminophen concentration during syrup manufacturing.

Main Methods:

• Development of a calibration set incorporating variability sources: production campaigns, batches, API concentration, syrup basis, operators, and sample temperatures.
• Construction of a prediction model using partial least square (PLS) regression with signal pre-processing (first derivative and standard normal variate - SNV).
• Validation of the model using an external validation set across API concentrations from 16 to 24 mg/mL (1.6-2.4%, w/v).

Main Results:

• A robust NIR calibration model was developed using 4 PLS factors, achieving a root mean square error of prediction (RMSEP) of 0.26 mg/mL.
• Accuracy profiles based on tolerance intervals confirmed the model's adequate performance across the investigated acetaminophen concentration range.
• Real-time monitoring of acetaminophen concentration during syrup mixing showed good agreement between NIR measurements and theoretical values.

Conclusions:

• The developed NIR model is a robust and accurate tool for quantifying acetaminophen in low-dose syrup formulations.
• The model demonstrates suitability for real-time process monitoring, enhancing quality control during syrup manufacturing.
• NIR spectroscopy, coupled with PLS regression, provides an effective analytical strategy for pharmaceutical quality assurance.