Analysis of Elemental Impurities in Medium- chain Triglycerides According to USP

Significance of the Topic

Medium-chain triglycerides (MCTs) serve as widely used pharmaceutical excipients due to rapid absorption and compatibility with oral formulations. Ensuring that these carrier oils comply with stringent limits for trace metal impurities is crucial to pharmaceutical quality and patient safety, especially under updated regulatory frameworks (USP<232>/<233>, ICH Q3D).

Objectives and Study Overview

This study compares two ICP-MS–based analytical routes for quantifying five specified heavy metals (Cr, Cu, Ni, Pb, Sn) in MCT samples, aligning with the revised USP Individual Test guidance and the broader USP<233> elemental impurity procedure. The aim is to validate both approaches against established recovery, precision, and detection criteria.

Methodology

The USP Individual Test method employs sequential wet digestion using sulfuric acid and hydrogen peroxide on a hotplate, followed by dilution and internal standard addition. The USP<233> protocol applies microwave-assisted digestion with a mixture of nitric and hydrochloric acids before similar post-digestion dilution and standardization. Calibration standards were prepared in acid matrices consistent with target elements.

Applied Instrumentation

Analysis utilized a Shimadzu ICPMS-2030 system equipped with collision cell technology. Key operating conditions included 1.2 kW RF power, 8.0 L/min plasma gas, 1.1 L/min auxiliary gas, and 0.7 L/min carrier gas. Helium collision gas flowed at 6.0 mL/min, and a mini torch with nickel sampling and skimmer cones ensured optimal sensitivity and matrix tolerance.

Main Results and Discussion

Both methods achieved recovery rates within the 80–120 % range for spiked samples, meeting USP validation criteria. The USP Individual Test delivered recoveries from 92 % to 120 % across the five target metals, with relative standard deviations usually below 5 %. The USP<233> method extended this performance to ten elements, recording recoveries between 88 % and 109 % and RSDs under 3.2 %. Notably, non-spiked MCT samples showed all analytes below detection limits, confirming the low intrinsic impurity content.

Benefits and Practical Applications

The validated ICP-MS protocols offer high sensitivity, robust accuracy, and streamlined workflows compared to legacy AAS techniques. They enable pharmaceutical laboratories to comply efficiently with current USP and ICH limits for elemental impurities, supporting quality control and regulatory submissions for drug products containing MCT excipients.

Future Trends and Opportunities

Advancements in collision/reaction cell technologies and automation are poised to further enhance detection limits and sample throughput. Emerging high-resolution MS systems and flow injection approaches may simplify prep steps and broaden the analyte scope, while harmonized global standards will reinforce method transferability across regulatory regions.

Conclusion

The ICPMS-2030 platform successfully quantifies trace heavy metals in MCTs under both USP Individual Test and USP<233> conditions, fulfilling validation benchmarks for recovery, precision, and detection. Adopting these ICP-MS–based methods supports reliable elemental impurity assessment in pharmaceutical excipients.

References

1. USP43-NF38, Medium-Chain Triglycerides, November 1, 2020.
2. European Pharmacopoeia 10th Edition, Triglycerides, Medium-Chain, 2019.
3. USP43-NF38 <232> Elemental Impurities—Limits and <233> Elemental Impurities—Procedures, November 1, 2020.
4. ICH Q3D(R1) Guideline for Elemental Impurities, March 22, 2019.