Assay of potassium carbonate and potassium bicarbonate

Importance of the Topic

Potassium carbonate (K2CO3) and potassium bicarbonate (KHCO3) are essential raw materials in pharmaceutical manufacturing, particularly in effervescent tablets and dietary supplements. Accurate quantification of each species is critical for ensuring patient safety, product efficacy, and compliance with pharmacopeial standards.

Objectives and Study Overview

This study describes a fully automated potentiometric titration assay for K2CO3 and KHCO3 according to USP <1225>. The goal was to develop a selective, reliable, and high-throughput method that meets system suitability, specificity, linearity, accuracy, precision, and sample analysis requirements.

Methodology and Instrumentation

No sample pretreatment is required. A defined sample mass is dissolved in carbonate-free deionized water and titrated with standardized HCl using an OMNIS platform. Key components include:

• OMNIS Sample Robot S with Dis-cover functionality
• OMNIS Dosing Module
• OMNIS Advanced Titrator equipped with dEcotrode Plus

Potentiometric detection provides two distinct equivalence points corresponding to the successive protonation steps (pKb ~8.3 and 3.69) of carbonate.

Results and Discussion

System suitability demonstrated RSD ≤0.5% over six replicates. Specificity tests by spike recovery confirmed distinct detection of each species; spiking KHCO3 with K2CO3 yielded a clear additional inflection. Linearity was excellent (R²≥0.9999) across 50–150% sample mass. Accuracy and precision at 80%, 100%, and 120% levels produced assay values within 100±2.0% of certificate of analysis (CoA) with RSD ≤1.0%. Intermediate precision (different electrode, day, and operator) also met criteria. Analysis of external batches matched manufacturer CoA values within specification.

Benefits and Practical Applications

This potentiometric assay offers:

• High selectivity without chromatographic separation
• Fully automated workflow for up to four parallel samples
• Improved throughput and reduced operator intervention
• Enhanced data integrity and 21 CFR 11 compliance

Future Trends and Potential Applications

Integration with laboratory information management systems (LIMS) and expansion to other acid–base pharmaceutical assays are anticipated. Ongoing advances in electrode design and automation will further streamline QA/QC processes and support real-time release testing.

Conclusion

The described potentiometric titration method reliably quantifies potassium carbonate and bicarbonate in pharmaceutical materials, meeting USP <1225> validation criteria. Automation improves accuracy, reproducibility, and regulatory compliance, making this approach a preferred alternative to manual or chromatographic techniques.

Instrumentation

• OMNIS Sample Robot S with Dis-cover
• OMNIS Dosing Module
• OMNIS Advanced Titrator with dEcotrode Plus

References

• USP General Chapter <1225>: Validation of Compendial Procedures
• European Pharmacopoeia, Monograph on Potentiometric Titration
• Metrohm Application Note T-210, Version 2 (2025-03)