Fast, Easy, and Reliable Measurements of Liquid Samples Using Transmission FTIR

Significance of the Topic

Transmission FTIR spectroscopy is crucial for quality control in pharmaceutical manufacturing. However, traditional transmission cells for liquid analysis are prone to errors due to pathlength inconsistency, fragility, leakage, air bubbles, and high solvent consumption. The Agilent DialPath module addresses these challenges by simplifying sample handling and improving data reliability.

Objectives and Study Overview

This study aimed to develop and validate a fast, easy, and reliable FTIR method for quantifying simethicone in liquid samples, comparing the performance of the Agilent Cary 630 FTIR fitted with the DialPath module against a traditional demountable transmission cell, following the USP43-NF38 monograph guidelines.

Methodology and Instrumentation

Standard, control, and commercial simethicone samples were prepared by dissolving simethicone in a 4.8 M HCl and toluene mixture, matching the 2 mg/mL reference concentration defined in USP43-NF38. All solutions underwent centrifugation and drying steps to remove water. Spectra were acquired over 4000 to 650 cm-1 with 64 background and sample scans, at 2 cm-1 resolution. A peak at ~1260 cm-1 was used for quantification via the MicroLab software, applying a multiplication factor to convert absorbance into percentage concentration.

Used Instrumentation

• Agilent Cary 630 FTIR spectrometer with DialPath module (pathlength 500 microns)
• Agilent Cary 630 FTIR spectrometer with demountable transmission cell (calcium fluoride windows, 500 micron spacer)
• Agilent MicroLab and MicroLab Quant software for data acquisition, quantitation, and calibration

Main Results and Discussion

Quantification of control samples showed that the DialPath provided accuracies between 98.1 and 100 % versus 97.4 to 98.8 % for the traditional cell. Commercial capsule measurements fell within the USP acceptance range (85–110 %) for both methods, with improved precision for the DialPath. Recovery tests using standard addition yielded recoveries around 100 % at 5, 10, and 15 % spikes. Calibration demonstrated excellent linearity up to 190 % simethicone (R2=0.9997). Repeatability studies showed a standard deviation of 0.0013 absorbance units and 0.34 % concentration. Throughput analysis indicated that the DialPath could process 40 samples per hour using only 20 µL per sample, compared to 20 samples per hour requiring 5 mL each with the transmission cell, significantly reducing solvent use and cleaning time.

Benefits and Practical Applications

• Enhanced reproducibility and data quality in simethicone quantification
• Reduction in sample volume and solvent waste
• Faster sample turnaround and simpler cleaning procedures
• Ease of use for nonexperts, supporting routine pharmaceutical QC

Future Trends and Potential Applications

Integration of transmission FTIR modules like DialPath into automated and online QC workflows can accelerate pharmaceutical analysis. Further miniaturization and coupling with advanced chemometric tools may broaden applications to other viscous or sticky samples. Expansion of software capabilities for compliance and data integrity can support regulatory requirements in global pharmacopeias.

Conclusion

The Agilent Cary 630 FTIR with the DialPath module delivers rapid, accurate, and precise quantification of simethicone in liquid formulations, with superior ease of use and resource efficiency compared to traditional transmission cells. This method meets USP performance criteria and offers significant time, cost, and solvent savings for pharmaceutical quality control laboratories.

Reference

• Simethicone Emulsion. United States Pharmacopeia and National Formulary USP43-NF38, page 4044, Agilent Technologies Application Note 5994-3046EN (2021)