Evaluating Repeatability and Sensitivity of Transmission Raman Spectroscopy

Significance of the Topic

Transmission Raman Spectroscopy is a light scattering technique that captures bulk structural information in solid dosage forms. Its ability to analyze entire tablets without destruction makes it highly valuable for uniformity content analysis in pharmaceutical quality control.

Study Objectives and Overview

This study evaluated the repeatability and sensitivity of the Agilent TRS100 system with respect to uniform content analysis of a drug containing 17% active pharmaceutical ingredient. Results were benchmarked against high performance liquid chromatography measurements.

Instrumentation

The Agilent TRS100 spectrometer used an 830 nm laser at 650 mW with a 4 mm diameter beam and a medium collection lens. Reference concentrations were determined by HPLC.

Methodology

Calibration standards spanning 85 to 115% of label claim (14.45 to 19.55% w/w API) were prepared gravimetrically and measured in twenty replicates each. Spectral preprocessing included trimming to 200–1800 cm-1, Whittaker baseline correction, area normalization and mean centering. A partial least squares model with one latent variable was built and validated by tenfold venetian blind cross validation.

Main Results and Discussion

The model achieved a calibration and cross validation R2 of 0.967 with RMSECV of 1.72% label claim. Repeatability assessment showed 96.6% of predictions within ±4% relative error of HPLC. Limits of detection and quantitation were 0.85 and 2.81% w/w API, respectively, demonstrating adequate sensitivity for quality control.

Benefits and Practical Applications

• Whole tablet analysis without sample destruction
• Rapid and direct quantification of API
• High throughput screening for uniformity content
• Reduced sample preparation and solvent use compared to HPLC

Future Trends and Potential Applications

Development of robust multivariate models for broader product ranges, calibration transfer strategies, inline or at line process analytical technology integration and extending TRS sensitivity toward lower dosage levels will further enhance its industrial applicability.

Conclusion

The Agilent TRS100 system demonstrates the repeatability and sensitivity required for uniform content analysis of solid dose pharmaceuticals, offering a fast, non-destructive alternative to HPLC for routine quality control.

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