Ion Chromatography Assay for Lithium in Lithium Citrate

Significance of the Topic

Ion chromatography offers a modern, automated approach to quantify lithium in pharmaceutical preparations, replacing manual, hazardous flame photometry and enabling multi-cation analysis in a single run.

Study Objectives and Overview

This work aimed to establish a robust IC method for determining lithium content in lithium citrate and to validate it following USP <1225> guidelines. The proposed assay addresses monograph modernization by combining speed, simplicity, and reproducibility.

Methodology and Instrumentation

A Thermo Scientific™ Dionex™ ICS-2100 RFIC system equipped with an EGC III MSA eluent generator, CR-CTC II trap column, and CERS 500 suppressor was employed. Separation used a Dionex IonPac CS12A-5µm (3×150 mm) column with a CG12A guard. The aqueous MSA eluent was delivered in a gradient (8→67→8 mM), at 0.4 mL/min and 33 °C, with a 10 µL injection volume. Stock and calibration standards (0.1–15 mg/L Li) were prepared from USP reference lithium carbonate and lithium citrate.

Main Results and Discussion

Separation achieved baseline resolution of lithium from sodium within a 20 min cycle. Calibration was linear (r² 0.9999) over 0.1–15 mg/L. LOD and LOQ were 1.2 µg/L and 4 µg/L, respectively. Precision (n=7) showed RT RSD ≤0.05% and area RSD ≤0.35%. Spike recoveries from lithium citrate solutions ranged 99.8–101.5%, confirming method accuracy. Robustness tests (±10% in flow rate, temperature, and eluent strength) demonstrated negligible shifts in retention, asymmetry, and resolution.

Benefits and Practical Applications

• Fully automated, reagent-free operation requiring only DI water
• Eliminates hazardous acids and flame photometry
• Simultaneous multi-cation analysis in a single injection
• Compliant with USP monograph modernization efforts

Future Trends and Opportunities

• Integration with online sample preparation and process analytics
• Extension to other lithium formulations and complex matrices
• Potential adoption in pharmacopeial monographs for broader standardization
• Advances in high-throughput and miniaturized IC platforms

Conclusion

This validated IC method provides a fast, sensitive, and environmentally friendly alternative to traditional assays for lithium in lithium citrate, aligning with current regulatory expectations and supporting routine QC laboratories.

References

• Choi SJ, Derman RM, Lee KS. Bipolar Affective Disorder, Lithium Carbonate and Ca²⁺ ATPase. J Affect Disord. 1981;3:77–79.
• U.S. Pharmacopeial Convention. Lithium Citrate. USP37–NF32. Rockville, MD: USP; 2014:3574.
• U.S. Pharmacopeial Convention. USP Seeks Submission of Proposals for Monograph Modernization. 2014. [Accessed October 31, 2014].
• Fritz JS, Gjerde DT, Becker RM. Cation Chromatography with a Conductivity Detector. Anal Chem. 1980;52:1519–1522.
• Validation of Compendial Methods, General Chapter <1225>. USP36–NF31. Rockville, MD: USP; 2013:983.
• Physical Tests, <621> Chromatography. USP36–NF31. Rockville, MD: USP; 2013:268.