ICP-MS ELEMENTAL IMPURITY ANALYSIS IN PHARMACEUTICALS

Importance of the Topic

Controlling elemental impurities in pharmaceuticals is vital to ensure patient safety and regulatory compliance. The transition from semi-quantitative colorimetric tests to fully quantitative analyses aligns with modern Quality by Design approaches and stringent safety mandates.

Objectives and Study Overview

This work demonstrates the implementation of ICH Q3D and USP <232>/<233> guidelines for quantifying 24 elemental impurities in drug substances and products. The focus is on evaluating the Agilent 7800/7900 ICP-MS system’s ability to meet regulatory “J” values and detection limits for highly toxic elements (As, Cd, Hg, Pb).

Methodology

A risk-based strategy guided sample preparation via acid digestion and dilution to match target analyte concentrations. Calibration standards ranged from 0.1 to 2.0 times each element’s “J” value. Helium collision mode eliminated common polyatomic interferences, while secondary isotopes provided confirmatory identification in compliance with USP <233>.

Used Instrumentation

• Agilent 7800/7900 ICP-MS equipped with ORS4 collision/reaction cell
• Helium mode for universal removal of polyatomic interferences
• High-temperature plasma and optimized ion transmission for ultra-low detection limits

Main Results and Discussion

Calibration curves for arsenic, cadmium, mercury, and lead exhibited excellent linearity (R > 0.999), with detection limits in the single-digit picogram-per-milliliter range. The He mode Quick Scan provided full elemental profiles—including extractables/leachables—within a single rapid sweep. The platform reliably quantified impurities at the low “J” values required for parenteral and inhalational products.

Benefits and Practical Applications

• Simultaneous quantitative determination of 24 regulated elements
• Direct analysis of raw materials, excipients, and finished dosage forms
• Supports risk-based impurity control and Quality by Design principles
• Efficient screening of packaging extractables and leachables

Future Trends and Potential Applications

Integration of HPLC-ICP-MS will allow species-specific toxicity assessments for elements like As and Hg. Ongoing developments in automation and miniaturized sample introduction promise near real-time monitoring of elemental impurities. Expansion of these methods to dietary supplements, biologics, and advanced drug delivery systems is anticipated.

Conclusion

The Agilent 7800/7900 ICP-MS platform fulfills the requirements of ICH Q3D and USP <232>/<233>, delivering high sensitivity, robust interference removal, and streamlined workflows for comprehensive elemental impurity analysis.