ANALYSIS OF EXTRACTABLE AND LEACHABLE METALS IN PLASTIC MATERIALS OF CONSTRUCTION AS PER USP <661.1> ACID EXTRACTION PROCEDURE USING THE AGILENT 5110 VDV ICP-OES

Significance of the Topic

The analysis of extractable and leachable metals in pharmaceutical packaging plastics is critical to ensure patient safety and regulatory compliance. Trace metals migrating from materials into drug products can impact efficacy, stability, and biocompatibility. Adhering to USP <661.1> guidelines for acid extraction and quantification helps manufacturers assess chemical safety and maintain product quality.

Objectives and Overview

This study demonstrates a complete solution for quantifying toxic and extractable trace metals in plastic construction materials using Agilent’s 5110 Vertical Dual View ICP-OES. Key objectives include:

• Implementing the USP <661.1> acid extraction protocol for high-density polyethylene (HDPE).
• Establishing calibration, method detection limits (MDLs), and spike recovery performance.
• Evaluating precision, repeatability, and method robustness for routine QC analysis.

Instrumentation

The core instrument is the Agilent 5110 VDV ICP-OES equipped with:

• Vertical torch enabling dual axial/radial viewing.
• VistaChip II high-speed CCD detector (167–785 nm, up to 8 orders of dynamic range).
• Single-pass glass cyclonic spray chamber with SeaSpray nebulizer and standard injector torch.
• Multimode Sample Introduction System (MSIS) for hydride-forming elements (As, Hg).
• SPS 4 autosampler and solid-state RF generator (27 MHz) for stable plasma.

Methodology and Instrumentation

Sample preparation followed the USP <661.1> acid reflux extraction:

• 100 g HDPE in 250 mL of 0.1 N HCl, refluxed for 1 h with stirring.
• Cooled extracts diluted to volume with 0.1 N HCl.
• Hydride elements pre-reduced (As: KI, NaBH₄, NaOH) and introduced via MSIS.
• All other elements measured in axial mode through the standard spray chamber.
• Calibration with multi-element NIST traceable standards.

Operating parameters included 1.20 kW RF power, 12 L/min plasma flow, 0.7 L/min nebulizer flow; read time 5 s, three replicates per sample.

Key Results and Discussion

Method detection limits ranged from 0.1 µg/L (Mn) to 4.0 µg/L (Ca). Calibration curves for As, Cr, Cd, and Pb showed excellent linearity. Spike recovery at two levels achieved between 95% and 110% with RSDs below 5% across all elements. Real HDPE extracts exhibited no detectable levels of toxic metals, confirming compliance with USP limits.

Benefits and Practical Applications

The Agilent 5110 VDV ICP-OES offers:

• High sensitivity and low MDLs for toxic metals profiling.
• Combined axial/radial viewing for robust, versatile measurements.
• Fast analysis times and reduced argon consumption.
• Reliable spike recovery and repeatability suitable for QC laboratories.

Future Trends and Opportunities

Advancements in analytical chemistry may include:

• Integration of hyphenated techniques (e.g., LC-ICP-MS) for speciation analysis.
• Enhanced automation and robotics for high-throughput extractables profiling.
• Development of novel plasma sources to further lower detection limits.
• Expansion of regulatory frameworks for broader material compatibility testing.

Conclusion

The Agilent 5110 VDV ICP-OES, combined with USP <661.1> extraction and MSIS, delivers a complete, sensitive, and robust workflow for extractable and leachable metal analysis in plastic pharmaceutical packaging. It meets regulatory expectations, offers high precision, and supports routine QC operations.

References

1. USP <661.1> Plastic Materials of Construction, effective May 1, 2016.
2. USP <661.2> Plastic Packaging Systems for Pharmaceutical Use, effective May 1, 2016.
3. USP <1663> Assessment of Extractables Associated with Pharmaceutical Packaging/Delivery Systems.
4. USP 34 General Notices and Requirements, May 1, 2011.