Analysis of ICH Q3D Guideline for Elemental Impurities in Drug Products Using ICPMS-2030

Importance of the Topic

Inductively coupled plasma mass spectrometry (ICP-MS) is a cornerstone for detecting trace elemental impurities in pharmaceutical products. Compliance with the ICH Q3D guideline, which specifies permitted daily exposures (PDEs) for 24 potentially toxic metals, is vital to safeguard patient health and meet regulatory requirements.

Objectives and Study Overview

The aim of this work was to develop and validate a rapid ICP-MS method using the Shimadzu ICPMS-2030 to quantify 24 elemental impurities in tablet dosage forms. Key steps include sample decomposition, calibration, and spike recovery testing to ensure accurate quantification below PDE limits.

Methodology

Tablets (0.20 g) were digested in quartz vessels with 0.5 mL HCl and 5 mL HNO3 using microwave pretreatment. Following digestion, 0.1 mL HCl was added and the solution was diluted to 20 mL, resulting in a 100-fold dilution. Internal standards (Sc, Ga, Y, Te at 10 µg/L) were added post-digestion. Calibration curves and internal standard methods were applied, along with spike-and-recovery tests to assess method accuracy.

Instrumentation

The Shimadzu ICPMS-2030 equipped with a mini-torch and cyclone chamber (electronic cooling) was used. Operating conditions included 1.2 kW RF power, plasma gas flow of 8.0 L/min, auxiliary gas at 1.1 L/min, and carrier gas at 0.60 L/min. A helium collision cell minimized argon and chlorine interferences. Eco mode and mini-torch operation reduced gas consumption and running costs.

Main Results and Discussion

All 24 elements were quantified with detection limits well below their respective PDE-based concentrations. Spike recovery values fell within acceptable ranges, demonstrating method accuracy. The helium collision system effectively suppressed common spectral interferences, enhancing data reliability.

Benefits and Practical Applications

• High sensitivity and specificity for a broad range of elements.
• Efficient sample preparation enabling high throughput.
• Reduced interference and lower operational costs through collision gas and Eco mode.
• Applicable to routine quality control and regulatory compliance testing in pharmaceutical laboratories.

Future Trends and Application Opportunities

Advancements may include automation of sample preparation, integration with online monitoring systems, expansion to complex formulations (e.g., injectables, biologics), and alternative collision gases to further reduce interferences. Coupling ICP-MS data with laboratory information management systems (LIMS) could streamline compliance reporting.

Conclusion

The presented ICP-MS method using the Shimadzu ICPMS-2030 provides a fast, accurate, and cost-effective approach for meeting ICH Q3D elemental impurity requirements in tablet products, ensuring product safety and compliance.

References

• Guideline for Elemental Impurities in Drug Products (PFSB/ELD Notification No. 4, September 30, 2015).
• ICH Q3D Guideline for Elemental Impurities (December 16, 2014), General Tests, Supplement to the Japanese Pharmacopoeia Sixteenth Edition.