Quantitative measurement of active pharmaceutical ingredients using the diffuse reflectance Cary 630 FTIR

Importance of the Topic

Fourier transform infrared (FTIR) spectroscopy is a cornerstone technique in pharmaceutical analysis, enabling both identification and quantification of active pharmaceutical ingredients (APIs) in solid and liquid forms. Accurate API measurement ensures product safety, efficacy and compliance with global pharmacopeial standards. Traditional KBr pellet methods are laborious and prone to variability, driving demand for faster, more reproducible approaches such as diffuse reflectance (DRIFT) and attenuated total reflectance (ATR).

Objectives and Study Overview

This application note evaluates the quantitative performance of the Agilent Cary 630 FTIR system using DRIFT sampling. A model formulation of acetaminophen in corn starch (0–10 % w/w) was prepared to establish calibration curves. Two sample protocols were compared: neat powders measured directly and powders diluted 1:10 in dry KBr, allowing assessment of dilution effects on spectral linearity and noise.

Methodology and Instrumentation

The Cary 630 FTIR features interchangeable ATR, DRIFT and DialPath liquid interfaces, housed in an ultracompact, robust platform. DRIFT sampling collects diffusely reflected infrared light from multiple particle interactions, enhancing sampling volume and reducing heterogeneity effects. Spectra were acquired with a 30 s collection time (74 scans) at 4 cm⁻¹ resolution.

Used Instrumentation

• Agilent Cary 630 FTIR spectrometer
• Diffuse reflectance sampling accessory
• 30 s collection time, 74 scans per spectrum
• 4 cm⁻¹ spectral resolution
• MicroLab PC software for data acquisition
• Resolutions Pro software for calibration development

Main Results and Discussion

Diluted samples yielded optimal absorbance (0.6–0.8 AU) for the 1559 cm⁻¹ acetaminophen band, normalized to the 1379 cm⁻¹ corn starch reference. Calibration showed excellent linearity (R² = 0.999). Neat powders were quantified by ratioing the 1559 cm⁻¹ band to a starch overtone near 2100 cm⁻¹, achieving perfect correlation (R² = 1.000). Dilution effectively suppressed noise from strongly absorbing excipient bands, while API signals remained within the linear range.

Benefits and Practical Applications

• Eliminates time-intensive KBr pellet preparation
• Delivers rapid, reproducible quantification of APIs in powders
• Supports both neat and diluted sample protocols
• Interchangeable interfaces streamline QA/QC and method development workflows

Future Trends and Potential Applications

Emerging FTIR detector technologies and advanced chemometric algorithms will enhance DRIFT’s sensitivity and selectivity for complex formulations. Integration with automated sampling systems and real-time data analytics can enable in-process monitoring and continuous manufacturing control. Adapting DRIFT for trace-level API detection and multivariate prediction models represents promising development areas.

Conclusion

The Agilent Cary 630 FTIR system with DRIFT sampling offers accurate, efficient quantitative analysis of pharmaceutical powders without pelletizing. Its robust performance for neat and diluted samples, combined with versatile sampling options, addresses critical industry needs in quality control and formulation analysis.