Measurement of Elemental Impurities in Pharmaceutical Products by ICP-AES and ETAAS

Importance of the Topic

The control of trace metal impurities in pharmaceutical products is essential for patient safety and regulatory compliance. Guidelines such as the Japanese Pharmacopoeia and USP chapters <232> and <233> define permissible limits for harmful elements (Pb, Cd, As, Hg) and recommend validated analytical methods. Reliable detection of these impurities at low levels helps ensure drug quality and supports global harmonization of safety standards.

Objectives and Study Overview

This study illustrates the determination of metallic contaminants in acetylsalicylic acid (aspirin) using two complementary techniques: inductively coupled plasma atomic emission spectrometry (ICP-AES) and electrothermal atomic absorption spectrometry (ETAAS). The goal was to evaluate method performance, verify compliance with pharmacopeial limits, and demonstrate suitability for routine QA/QC in pharmaceutical analysis.

Methodology and Instrumentation

Sample Preparation:

• Approximately 0.5 g of aspirin was digested using a closed-vessel microwave system (ETHOS One) to prevent loss of volatile metals.
• Nitric and hydrochloric acids were used for digestion, followed by near-dryness treatment and pre-reduction for arsenic hydride generation.

ICP-AES Conditions:

• Instrument: Shimadzu ICPE-9000 with Echelle spectrometer and CCD detector.
• RF Power: 1.2 kW; Plasma gas 10 L/min; Auxiliary gas 0.6 L/min; Carrier gas 0.7 L/min.
• Mini torch and coaxial nebulizer for reduced argon consumption.
• Internal standard correction with Yttrium; hydride generation for arsenic.

ETAAS Conditions:

• Instrument: Shimadzu AA-7000 with GFA-7000 graphite furnace.
• Analytes: Arsenic (193.7 nm) and Lead (283.3 nm).
• Matrix modifier: Palladium nitrate for As; D2 background correction.
• Ashing/atomization temperatures optimized (As: 800 °C/2200 °C; Pb: 600 °C/2000 °C).

Key Results and Discussion

Neither target element exceeded detection limits in unspiked samples. Spike-and-recovery tests demonstrated accuracy and precision:

• ICP-AES recoveries ranged from 91 % to 109 % across 14 elements.
• ETAAS recoveries for As and Pb were 95 % and 100 %, respectively.

Detection limits were well below pharmacopeial thresholds. ICP-AES allowed simultaneous multi-element analysis for efficient screening, while ETAAS provided enhanced sensitivity for key toxic elements.

Benefits and Practical Applications

The combined use of ICP-AES and ETAAS offers:

• Comprehensive multi-element screening with high throughput.
• Cost savings from reduced argon usage with a mini torch.
• Low-volume, high-sensitivity measurements for regulatory compliance.
• Flexibility to target both major and trace contaminants in pharmaceutical QA/QC.

Future Trends and Opportunities

Advancements may include further miniaturization of plasma sources, integration of online sample preparation, and coupling to mass spectrometry for even lower detection limits. Automation and data analytics will streamline workflows and support real-time quality monitoring in pharmaceutical manufacturing.

Conclusion

This work demonstrates that ICP-AES and ETAAS are robust, validated techniques for trace metal analysis in pharmaceutical products. Both methods satisfy pharmacopeial requirements, offering accurate, efficient, and cost-effective solutions for ensuring drug safety.

References

• Shimadzu Application Note No. J98, "Measurement of Elemental Impurities in Pharmaceutical Products by ICP-AES and ETAAS," First Edition March 2013.
• Japanese Pharmacopoeia Notification No. 1216001 (2002), first revision of the 16th edition (2012).
• United States Pharmacopeia <232> and <233>, Elemental Impurities – Limits and Procedures.