Analysis of elemental impurities in drug products using the Thermo Scientific iCAP 7400 ICP-OES Duo

Significance of the Topic

Elemental impurities in pharmaceuticals pose health risks and can affect product stability and shelf-life. Compliance with regulatory guidelines such as USP <232>, <233> and ICH Q3D ensures patient safety by controlling daily exposure to toxic metals.

Objectives and Study Overview

This work demonstrates an ICP-OES–based procedure for quantifying 24 elemental impurities in drug products, validating compliance with USP General Chapters <232> (Limits) and <233> (Procedures) under 21 CFR Part 11. The method was applied to an acetylcysteine effervescent tablet as a model sample.

Methodology and Instrumentation

• Instrument: Thermo Scientific iCAP 7400 ICP-OES Duo with aqueous sample introduction kit and CETAC ASX-560 autosampler.
• Internal standard: Yttrium at 5 mg/kg via online addition.
• Calibration: Two multi-element stock solutions prepared in 5% HCl; J values calculated from PDE, daily dose and dilution factor.
• Parameters: Optimized axial and radial views, spray chamber, nebulizer flow, RF power and exposure times.
• Sample preparation: Effervescent tablet dissolved in ultrapure water, acidified to 5% HCl, spiked and diluted to 50 mL.

Main Results and Discussion

• Accuracy: Spike recoveries at 0.5 J and 1.5 J ranged from 86% to 109%, within the 70–150% acceptance.
• Precision: Repeatability (n=6) RSDs 0.7–2.5%, ruggedness (n=12) RSDs 1.5–6.0%, all below 20% and 25% thresholds.
• Specificity: Dual wavelengths per analyte confirmed absence of spectral interferences.
• System suitability: Drift between initial and final standards remained below 5%, meeting USP criteria.

Benefits and Practical Applications

The validated ICP-OES method enables rapid, simultaneous determination of multiple metal impurities in pharmaceuticals, streamlining quality control while meeting regulatory mandates. Its low detection limits allow reliable monitoring of critical elements like arsenic and mercury at sub-µg/kg levels.

Future Trends and Prospects

Advances in plasma spectrometry, enhanced software for spectral deconvolution and automated sample handling are expected to further improve throughput and sensitivity. Emerging ICP-MS technologies and new chemometric tools may extend capabilities for speciation and ultra-trace analyses.

Conclusion

The Thermo Scientific iCAP 7400 ICP-OES Duo reliably quantifies elemental impurities per USP <232>/<233> and ICH Q3D, offering robust performance in accuracy, precision and specificity for pharmaceutical quality assessment.

References

1. USP <232> Elemental Impurities—Limits, USP 40-NF 35, First Supplement.
2. USP <233> Elemental Impurities—Procedures, USP 38-NF 33, Second Supplement.
3. ICH Q3D Impurities: Guideline for Elemental Impurities, Step 4 Version (2014).
4. USP <2232> Elemental Contaminants in Dietary Supplements, USP 38-NF 33, Second Supplement.
5. 21 CFR 11, Electronic Records; Electronic Signatures (2017).