Ferrous iron in iron sucrose injection

Significance of the Topic

Iron sucrose injections play a critical role in treating iron deficiency anemia by delivering bioavailable iron directly into the bloodstream. Precise quantification of ferrous iron (Fe2+) in these preparations is essential for dosage accuracy, safety, and regulatory compliance. Traditional approaches that calculate Fe2+ by difference or employ potentiometric titration can suffer from increased error or ambiguous endpoints, highlighting the need for a more robust analytical technique.

Objectives and Study Overview

This study aimed to establish a rapid, reliable, and matrix-independent method for direct determination of Fe2+ in iron sucrose injections using thermometric titration. Key goals included:

• Developing a straightforward sample preparation to minimize oxidation of Fe2+.
• Optimizing titration conditions to ensure a distinct and reproducible endpoint.
• Comparing performance with conventional potentiometric methods in terms of speed, precision, and ease of use.

Methodology and Instrumentation

An 859 Titrotherm system equipped with a fast-responding Thermoprobe and controlled by tiamo™ software was employed. Sample preparation involved combining multiple ampoules under nitrogen, spiking with 0.2% ferric ammonium sulfate to sharpen the exothermic endpoint, acidifying with dilute sulfuric acid, and diluting to 30 mL. Titration was performed against standardized ceric ammonium nitrate until an exothermic peak indicated the endpoint.

Used Instrumentation:

• 859 Titrotherm complete with tiamo™ including Thermoprobe and 10 mL buret
• 800 Dosino drive with intelligent dosing units
• Dosing units for 5 mL and 10 mL reagent delivery

Main Results and Discussion

Titrations of three independent batches yielded consistent Fe2+ contents of 0.238 %, 0.220 %, and 0.227 %, with absolute standard deviations below 0.007 %. The thermometric curves showed a sharp exothermic peak, facilitating unambiguous endpoint detection within 2–3 minutes. Compared to potentiometric titration, the thermometric approach eliminated the need for dual measurements and sensor maintenance, reducing overall analysis time and potential sources of error.

Benefits and Practical Applications

The thermometric titration method offers several advantages:

• Rapid analysis with each determination completed in under three minutes.
• High precision and reproducibility, unaffected by sample matrix components.
• Minimal instrument maintenance: the Thermoprobe requires no conditioning or replacement.
• Simplified workflow: a single titration suffices to quantify Fe2+ directly.

This approach is well suited for routine quality control in pharmaceutical manufacturing and regulatory testing laboratories.

Future Trends and Opportunities

Emerging prospects include:

• Extending thermometric titration to other transition metal quantifications in complex formulations.
• Integration with online process control systems for real-time monitoring of iron dosing in production lines.
• Miniaturization of the thermometric sensor for field applications or point-of-care testing.

Conclusion

Thermometric titration with ceric ammonium nitrate provides a robust, rapid, and maintenance-free technique for direct determination of Fe2+ in iron sucrose injections. The method delivers clear, reproducible endpoints and streamlines routine analysis by avoiding the pitfalls of indirect or potentiometric approaches.

References

Metrohm AG, Application Note AN-H-144: "Ferrous iron in iron sucrose injection – Rapid and reliable determination by thermometric titration."