Karl Fischer titration and near-infrared spectroscopy in perfect synergy

Importance of the topic

Accurate water content determination is essential across pharmaceuticals, chemicals, food, and petroleum industries to ensure product quality, stability, and compliance with regulations. Karl Fischer titration provides highly selective determination of water, while near-infrared spectroscopy (NIRS) offers rapid, non-destructive analysis with minimal sample preparation. Combining these two complementary methods enhances laboratory productivity and data confidence.

Objectives and overview of the study

This white paper describes recent developments in moisture analysis and demonstrates how NIRS calibration models based on Karl Fischer titration data can accelerate routine water determinations. The goal is to achieve high throughput without compromising analytical accuracy.

Methodology and instrumentation used

• Karl Fischer titration: Coulometric titration for low water levels (0.001–1 %) and volumetric titration for higher moisture (0.1–100 %). Sample introduction via syringe into a methanol-based reagent system; endpoint detection by polarized double platinum electrode.
• Near-infrared spectroscopy: Direct measurement of powders, liquids, and creams in disposable glass vials, cuvettes, or slurry cups. Data acquisition under Vision Air 2.0 software, followed by chemometric model development using Partial Least Squares Regression (PLS).

Main results and discussion

A robust calibration model relating NIR spectral features to KF-determined water contents was established and validated, demonstrating comparable accuracy to titration. Routine NIRS analysis requires fewer than 60 seconds per sample, including automated wavelength standardization. Periodic concordance tests against Karl Fischer titration ensure ongoing reliability.

Benefits and practical applications

• Significant increase in sample throughput by replacing lengthy titrations with rapid NIRS measurements.
• No chemical reagents or extensive sample preparation needed for NIRS.
• Versatile implementation in QC, R&D, and production laboratories for various sample types.
• Simultaneous prediction of multiple quality parameters beyond moisture.

Future trends and opportunities

Advancements in chemometric algorithms will improve model robustness and extend applicability to complex matrices. The integration of at-line and online NIRS sensors can enable real-time process monitoring. Miniaturized NIR instruments and automated data workflows promise further gains in efficiency and reproducibility.

Conclusion

The synergistic use of Karl Fischer titration and near-infrared spectroscopy combines the selectivity and accuracy of titration with the speed and convenience of NIRS. This dual-method approach ensures robust water determinations and supports high-throughput analytical environments.

Reference

• Metrohm White Paper WP-023EN, October 2017