Determining Elemental Impurities in Pharmaceutical Ingredients using ICP-MS

Significance of the Topic

The control of elemental impurities in pharmaceutical ingredients is critical to ensure patient safety, product stability, and regulatory compliance. USP <232>/<233> and ICH Q3D define permitted daily exposures (PDEs) for 24 elements. Reliable quantification methods are needed to monitor raw materials, APIs, excipients, and process-related contaminants.

Objectives and Study Overview

This study evaluates a streamlined ICP-MS procedure for measuring 24 elemental impurities in pharmaceutical powders dissolved in dimethyl sulfoxide (DMSO). The goal is to demonstrate compliance with USP <233> and ICH Q3D while improving throughput and ease of use compared with acid digestion.

Methodology and Instrumentation

• Sample Preparation: Accurately weigh 100 mg of API, add 5 mL DMSO, sonicate 15 min, dilute to 50 mL with DMSO; prepare unspiked and spiked replicates.
• Instrumentation: Agilent 7800 ICP-MS (also compatible with 7850/7900) with MicroMist nebulizer, peltier-cooled quartz spray chamber at 17 °C, 1.5 mm torch injector, platinum cones, ORS4 collision/reaction cell, argon-oxygen optional gas, and SPS 4 autosampler.
• Operating Conditions: RF Power 1550 W; nebulizer gas 0.99 L/min; optional gas 10%; sample depth 8 mm; helium cell gas 4 mL/min; energy discrimination 3 V.
• Calibration: NIST-traceable standards in DMSO yielded linearity (R>0.995) and detection limits in the low ng/L range for all elements.
• System Suitability: Drift <20% over 4 h; spike recoveries 90–110%; precision (%RSD) within acceptance limits; intermediate precision <10% for most elements.

Main Results and Discussion

The DMSO-based method achieved high sensitivity, robust stability, and minimal matrix effects. Calibration and system suitability tests confirmed accurate quantification at PDE levels. Spike recovery experiments in three API matrices produced recoveries within 90–110% and %RSD<10%. No significant carbon deposition or spectral interferences were observed.

Benefits and Practical Applications

• Eliminates lengthy closed-vessel microwave acid digestions.
• Requires small sample volumes and less reagent consumption.
• Facilitates high sample throughput and simplified workflow.
• Aligns with USP/ICH regulations and is easily implemented in QC laboratories.

Future Trends and Potential Uses

DMSO-based dissolution may be extended to complex formulations, biologics, and dosage forms. Automation of sample handling and advanced data analytics, including AI-driven interpretation, can further enhance throughput and data quality. Continued collision/reaction cell development will support broader elemental coverage and lower detection limits.

Conclusion

The Agilent 7800 ICP-MS paired with DMSO dissolution provides a compliant, efficient, and reliable solution for determining elemental impurities in pharmaceutical ingredients. This approach enhances laboratory productivity, reduces analysis time, and meets stringent regulatory requirements.

References

1. USP Chapter <232> Elemental Impurities–Limits, Pharmacopeial Forum, 42(2), Mar–Apr 2016.
2. USP Chapter <233> Elemental Impurities–Procedures, USP 38–NF 33, Second Supplement.
3. ICH Guideline Q3D on Elemental Impurities, EMA/CHMP/ICH/353369/2013, July 2016.