TOC System Suitability Test for Sterile Water According to USP

Importance of the Topic

Ensuring the purity of sterile water in pharmaceutical and biotech applications is critical for patient safety and product quality. Total Organic Carbon (TOC) analysis is a key quality control measure mandated by the United States Pharmacopeia (USP) to monitor organic impurity levels in water used for injection and other sterile preparations.

Aims and Overview of the Study

This application note demonstrates the USP TOC system suitability test for sterile water and verifies the capability of a combustion catalytic oxidation TOC analyzer to quantify low-level organic carbon (<0.10 mg/L). The study follows USP guidelines for system performance and lower limit quantitation using standard solutions.

Methods and Instrumentation

Two USP standard substances are employed:

• Sucrose solution (8 mgC/L) as the reference sample
• 1,4-Benzoquinone solution (8 mgC/L) as the system suitability test solution

The Shimadzu TOC-L CPH Total Organic Carbon Analyzer is used throughout. Key measurement parameters:

• Catalyst: High-sensitivity combustion catalytic oxidation
• Detection mode: NPOC via acidification and sparging
• Injection volume: 51 µL for system suitability; 500 µL for low-level quantitation
• Calibration: Two-point (0–8.0 mgC/L) for system suitability; five-point (0–0.1–0.5–1.0–2.0 mgC/L) for low-level measurements

Main Results and Discussion

System suitability testing yielded the following:

• Blank distilled water TOC: 0.063 mg/L
• Sucrose standard TOC: 8.087 mg/L
• Benzoquinone test TOC: 8.007 mg/L
• Calculated recovery: 99.0 %, within the USP acceptance range of 85 %–115 %

Low-level quantitation at 0.0987 mgC/L showed:

• Measured value: 0.0987 mgC/L
• Coefficient of variation (CV): 4.31 % (below the 10 % threshold)

These results confirm that the TOC-L CPH analyzer meets USP requirements for both system suitability and sensitivity down to 0.10 mg/L TOC.

Benefits and Practical Applications

By demonstrating robust recovery and precision, this method supports routine quality control in pharmaceutical water systems. Laboratories can rely on the Shimadzu TOC-L CPH analyzer for:

• Regulatory compliance with USP TOC limits
• Accurate monitoring of organic impurities in water for injection
• Assurance of instrument performance through standardized system suitability testing

Future Trends and Opportunities

Advances in TOC analysis may include:

• Enhanced catalyst materials for lower detection limits
• Automated inline monitoring for continuous water quality assurance
• Integration with data management systems for real-time compliance reporting

Conclusion

The Shimadzu TOC-L CPH combustion catalytic oxidation analyzer effectively fulfills USP requirements for sterile water TOC analysis, delivering reliable recovery rates and precise low-level quantitation. Its performance ensures robust quality control for pharmaceutical water systems.

References

1. United States Pharmacopeia, TOC System Suitability Test for Sterile Water.
2. Shimadzu Corporation, Application No. O51, First Edition, January 2015.