Determination of Ammonia in Sodium Bicarbonate

Significance of the Topic

Sodium bicarbonate is a key ingredient in pharmaceutical and food products, notably as a buffer in hemodialysis solutions. Trace levels of ammonia in sodium bicarbonate must be rigorously controlled, since elevated ammonia can lead to adverse physiological effects. Traditional colorimetric assays for ammonia suffer from subjectivity, handling hazards, and potential for hazardous byproducts. An ion chromatography (IC) approach offers enhanced sensitivity, specificity, and safety for quality control of hemodialysis-grade sodium bicarbonate.

Goals and Study Overview

The study aimed to develop a robust IC-based method to quantify ammonia in sodium bicarbonate at or below the USP limit of 0.002% (w/w). Validation followed USP General Chapter <1225> and ICH guidelines, assessing linearity, precision, accuracy, detection and quantitation limits, and ruggedness under deliberate variations of analytical parameters.

Methodology and Instrumentation

The assay utilized a Thermo Scientific Dionex ICS-5000+ HPIC system with SP pump, EG eluent generator, and CD conductivity detector under autosuppression mode. A guard and analytical Dionex IonPac CS16 column pair separated sodium and ammonium ions. Eluent was 7 mM methanesulfonic acid (MSA) for initial separation, ramped to 70 mM MSA, then re-equilibrated. Sample preparation involved diluting a 25 mg/mL sodium bicarbonate monograph solution to 1 mg/mL, spiked with known ammonia levels. Calibration standards ranged from 0.02 to 2 mg/L ammonia in water.

Main Results and Discussion

The CS16 column achieved baseline resolution of ammonia from sodium (resolution >5, peak asymmetry ≈1.2) despite a 50 000:1 sodium-to-ammonium ratio. Method precision yielded retention time RSDs <0.06% and peak area RSDs <2.5%. Accuracy studies over three days at three spike levels (0.02, 0.1, 0.5 mg/L) produced recoveries of 77–85%. Using proposed signal-to-noise measurement (peak-to-peak), the limit of detection and quantitation for ammonia were 0.001 and 0.003 mg/L, respectively. Linearity was maintained over 0.02–2 mg/L with a quadratic fit (R2=0.9998). Robustness tests altering flow rate, column temperature, eluent concentration, and column batches confirmed stable retention, resolution, and peak shape.

Benefits and Practical Applications of the Method

• Enhanced sensitivity and specificity for ammonia in high-sodium matrices
• Automated eluent generation and self-regenerating suppressor increase safety and reproducibility
• Reduced use of hazardous reagents and elimination of cyanide gas risk
• Compliance with USP and ICH performance criteria for compendial methods

Future Trends and Opportunities

Further integration of IC with mass spectrometry could expand detection capabilities to other low-level cationic impurities. Miniaturized and high-throughput IC systems may support real-time monitoring in continuous production. Advances in suppressor technology and eluent generation will drive greener, fully automated workflows in pharmaceutical quality control.

Conclusion

The presented IC method reliably quantifies trace ammonia in sodium bicarbonate at pharmacopeial limits. It offers significant improvements over colorimetric assays in sensitivity, safety, and robustness, fulfilling regulatory validation requirements and supporting quality assurance in hemodialysis-grade products.

References

• U.S. Pharmacopeia. Sodium Bicarbonate Monograph. USP35, Rockville MD.
• European Pharmacopoeia. Sodium Hydrogen Carbonate. Ph. Eur. 7.0.
• U.S. Pharmacopeia. General Chapter <1225> Validation of Compendial Methods. USP/NF.
• ICH. Validation of Analytical Procedures: Text and Methodology. Q2(R1).
• U.S. Pharmacopeia. General Chapter <621> Chromatography. USP34/NF29.
• Hinshaw JV, Dolan JW. Pharmacopeial Forum 2012;38(3):Signal-to-Noise Measurements.
• Thermo Scientific. Salt-Converter Cation Self-Regenerating Suppressor 300 Data Sheet.
• Thermo Scientific. Application Note 1072: IC Assay for Ammonia in Adenosine.