Automated moisture analysis in pharmaceutical peptides

Significance of the Topic

Lyophilized pharmaceutical peptides require precise moisture control to ensure stability, efficacy, and safety. Residual moisture affects product shelf life and performance, making reliable moisture analysis essential in process control, stability studies, and optimization of the freeze-drying process.

Study Objectives and Overview

This work evaluates near-infrared spectroscopy (NIRS) as a rapid, reagentless alternative to Karl Fischer titration for quantifying residual moisture in lyophilized peptides. The study compares NIRS predictions to standard titration results across multiple samples to assess accuracy and robustness.

Methodology and Instrumentation

• NIRS XDS Interactance OptiProbe Analyzer: robust spectroscopic system for reflectance and immersion measurements under processing conditions.
• 815 Robotic USB Sample Processor XL: automated sample handling enabling high-throughput analysis of up to 62 samples per run.
• Vision Air 2.0 Complete software: integrated platform for method development, instrument control, and data management in regulated environments.
• tiamo™ 3.0 light: software for controlling titration reference measurements.

Seventeen peptide samples with varying moisture levels were measured. Karl Fischer titration provided reference moisture values. Spectral data underwent second derivative preprocessing, outlier detection, and partial least squares (PLS) calibration with an independent validation set.

Main Results and Discussion

The NIRS model achieved excellent agreement with Karl Fischer titration, yielding a correlation coefficient (R2) of 0.99. Calibration and validation standard errors (SEC and SEV) were 0.054% and 0.061% moisture, respectively, demonstrating high sensitivity and predictive accuracy. These results confirm the suitability of NIRS for non-destructive moisture quantification.

Benefits and Practical Applications

• Rapid, real-time moisture determination without reagents.
• Non-destructive analysis preserving sample integrity.
• High-throughput capability with automated sample handling.
• Cost-effective and environmentally friendly compared to titration.
• Integration into routine quality control and process analytical technology (PAT) workflows.

Future Trends and Potential Applications

Advancements in chemometric algorithms and miniaturized NIR probes will expand in-line and at-line monitoring capabilities. Integration with artificial intelligence and continuous manufacturing platforms will further enhance process control. Potential applications include broader biologics, biotechnology processes, and real-time stability monitoring.

Conclusion

NIRS provides a fast, accurate, and non-destructive method for moisture analysis in lyophilized peptides, offering a viable alternative to Karl Fischer titration for routine quality control and process optimization.

References

• Metrohm AG. Application Note AN-NIR-078: Automated moisture analysis in pharmaceutical peptides.