Determination of nitrogen content

Significance of the Topic

The Kjeldahl method remains a cornerstone technique for quantifying total nitrogen content in both organic and inorganic materials, playing a critical role in quality control, regulatory compliance, environmental monitoring, and nutritional analysis.

Objectives and Overview of the Study

This application note demonstrates an automated approach to determine the nitrogen content of heparin sodium in accordance with the United States Pharmacopeia (USP) general chapter <461> using a modern titration platform.

Methodology and Instrumentation

The procedure comprises three main steps:

• Digestion – conversion of organic nitrogen to ammonium using sulfuric acid, potassium sulfate, and copper sulfate catalysts
• Distillation – addition of sodium hydroxide to convert ammonium to ammonia, followed by steam distillation into a boric acid absorbing solution
• Titration – potentiometric titration of the absorbed ammonia with standardized sulfuric acid to determine the nitrogen content

Used Instrumentation

• 905 Titrando high-end potentiometric titrator with up to four Dosino dosing units
• 900 Touch Control or PC control via tiamo software
• iUnitrode combined pH electrode with integrated temperature sensor

Main Results and Discussion

The measured nitrogen content of heparin sodium was 1.581% (relative standard deviation 1.48%, n=5), which falls within the USP specification range of 1.3% to 2.5%. The titration curves exhibited sharp inflection points, enabling precise endpoint detection and high reproducibility.

Benefits and Practical Applications

This automated Kjeldahl titration method delivers accurate, reliable, and efficient nitrogen determination suitable for:

• Pharmaceutical compounds such as antithrombin III, enoxaparin sodium, and mecamylamine hydrochloride tablets
• Biopolymers and excipients including dextran, cellulose derivatives, and povidone
• Food and nutritional products like spirulina tablets, wheat bran, and guar gum
• Industrial polymers and dispersions such as polyvinyl acetate dispersion and crospovidone

Future Trends and Potential Applications

Ongoing developments may include increased automation, miniaturized digestion systems, coupling with spectroscopic detectors, integration into digital laboratory workflows, extension to environmental and food safety testing, and adoption of greener reagent alternatives.

Conclusion

The automated Kjeldahl determination using the Titrando platform provides a robust, precise, and compliant solution for nitrogen analysis across diverse sample types, streamlining quality assurance in pharmaceutical and industrial laboratories.

Reference

• United States Pharmacopeia General Chapter <461>, Nitrogen determination by Kjeldahl Method
• Metrohm Application Note AN-T-195, Determination of nitrogen content – Kjeldahl determination according to USP general chapter <461>