Analysis of Extractable and Leachable Metals in Plastic Materials used for Drug Products by ICP-OES

Importance of the Topic

Plastic packaging materials in pharmaceuticals can leach trace metals, posing safety and regulatory concerns. USP <661.1> mandates profiling of extractable and leachable metals in polymers like HDPE to ensure drug product integrity and patient safety.

Objectives and Study Overview

This application note presents a validated ICP-OES method using an Agilent 5110 VDV instrument to quantify extractable metals in HDPE per USP <661.1>. The study targets hazardous elements such as As, Cd, Hg, Pb, and others, demonstrating compliance with regulatory limits.

Methodology and Instrumentation

• Sample Preparation: Three 100 g HDPE samples refluxed in 0.1 N HCl for 1 h and diluted to 250 mL.
• Calibration: Multi-element NIST-traceable standards; two spike levels (0.025 and 0.05 mg/L; Ca at 0.25 and 0.5 mg/L).
• Instrumentation: Agilent 5110 VDV ICP-OES with solid-state RF, axial viewing; MSIS for hydride elements (As, Hg).
• Operating Conditions: 1.2 kW RF power; 12 L/min plasma flow; 0.7 L/min nebulizer; 5 s read time; three replicates; fitted background correction.

Main Results and Discussion

• MDLs: Established by 10 blank replicates; all MDLs (e.g., As 0.5 µg/mL, Cd 0.3 µg/mL, Hg 0.2 µg/mL) fall below USP <661.1> limits.
• HDPE Analysis: No measured metal exceeded the “Not More Than” concentration limits.
• Spike Recoveries: 97–110% with RSDs <3.5%, confirming method accuracy and precision.

Practical Benefits and Applications

• Regulatory Compliance: Supports early adoption of USP <661.1> requirements for plastic materials.
• High Throughput: Automated autosampler and fast analysis improve laboratory efficiency.
• Comprehensive Coverage: Single-instrument solution for trace and ultra-trace metals, including hydride-forming species.

Future Trends and Applications

• Extension to Other Polymers and Full Packaging Systems per USP <661.2>.
• Enhanced Detection: Integration of advanced detectors and refined sample introduction to lower detection limits further.
• Data Integration: Coupling ICP-OES results with digital data management and chemometrics for real-time quality monitoring.

Conclusion

The Agilent 5110 VDV ICP-OES method, paired with MSIS for hydride elements, delivers robust, sensitive, and precise quantitation of extractable metals in HDPE. MDLs are well below regulatory thresholds, and high recoveries demonstrate suitability for routine compliance testing.

References

1. USP 39–NF 34 <661.1> Plastic Materials of Construction, United States Pharmacopeia, 2016.
2. USP 39–NF 34 <661.2> Plastic Packaging Systems for Pharmaceutical Use, United States Pharmacopeia, 2016.
3. USP Revision Bulletin, Plastic Materials of Construction, March 2021.