Validation of Analysis Method Using ICPMS-2030 Based on USP <233> ELEMENTAL IMPURITIES - PROCEDURES

Significance of the Topic

The control of elemental impurities in pharmaceuticals is critical to ensure patient safety and regulatory compliance. The ICH Q3D guideline and USP <233> set stringent Permitted Daily Exposure (PDE) limits for 24 elements. Reliable analytical methods are essential for monitoring trace metals at levels well below these thresholds, supporting quality assurance in drug manufacturing.

Study Objectives and Overview

This study validates an ICPMS-2030 method following USP <233> procedures to quantify 24 elemental impurities in oral drug ingredients. Using Tosufloxacin Tosylate Monohydrate as the test sample, the work assesses method accuracy, precision, limit of quantitation, and specificity under a control threshold of 10% PDE to demonstrate robustness at low concentration levels.

Methodology and Instrumentation

A microwave digestion system (Multiwave PRO) was used to decompose 0.2 g of sample with nitric acid, hydrochloric acid, and ultrapure water, then diluted 250× to a final volume of 50 mL. Stability conditions for osmium required alternative digestion settings.

• Instrumentation Used
  • ICPMS-2030 with mini-torch and cyclonic chamber
  • Helium collision gas and automatic internal standard addition kit
• Internal Standards: Be, Bi, Ga, Sc, Tb, Te, Y
• Plasma Conditions: RF power 1.2 kW; plasma gas 8.0 L/min; auxiliary gas 1.1 L/min; carrier gas 0.7 L/min

Main Results and Discussion

Accuracy and precision were evaluated at 50%, 100%, and 150% of the target concentration (J). Acceptance criteria were 70–150% recovery and RSD ≤ 20%. Results showed:

• Spike recovery between 94% and 105%
• Repeatability RSD from 0.5% to 3.9%
• Quantitation limits confirmed at 50% concentration

Specificity tests addressed isobaric and polyatomic interferences:

• ArCl interference with As (m/z 75) was eliminated using helium collision gas
• MoO interference on Cd (m/z 111) was effectively removed by combining collision gas with interelement correction

Benefits and Practical Applications

This validated method enables pharmaceutical laboratories to:

• Detect and quantify 24 critical elemental impurities at low µg/g levels
• Meet USP <233> requirements for oral drug products
• Utilize standard ICP-MS equipment with minimal additional sample pretreatment

Future Trends and Applications

Advances in collision/reaction cell technology and data processing may further lower detection limits and simplify interference correction. Integration with automated sample introduction and software-driven method optimization will enhance throughput, supporting continuous monitoring of elemental impurities in complex matrices.

Conclusion

The Shimadzu ICPMS-2030 method fulfills USP <233> criteria for accuracy, precision, quantitation limit, and specificity at control levels of 10% PDE. Use of helium collision gas and interelement correction ensures reliable quantitation in the presence of common interferences. This approach offers a robust solution for routine elemental impurity testing in pharmaceutical quality control.

References

1. ICH Q3D Guideline for Elemental Impurities (R1)
2. United States Pharmacopeia General Chapter <233> Elemental Impurities—Procedures