Analysis of Residual Catalysts in Pharmaceuticals Using ICP Atomic Emission Spectrometry

Significance of the Topic

Pharmaceutical formulations often contain residual metal catalysts from synthesis that pose health risks and are regulated by agencies such as EMEA, USP and ICH Q3C.

Objectives and Study Overview

This study evaluates the use of inductively coupled plasma atomic emission spectrometry (ICP-AES) to quantify 14 metal impurities in drug substances according to EMEA guidelines. It demonstrates Shimadzu ICPE-9000 features, method validation, and analysis of real pharmaceutical samples.

Methodology and Instrumentation

ICP-AES transforms samples into argon plasma at 6000–8000 K, exciting elements to emit characteristic wavelengths for quantitative analysis. Shimadzu ICPE-9000 employs a multichannel echelle prism spectrometer with a 1 MP CCD detector, a vacuum optical system, and automated axial/radial view switching. Sample preparation uses DMSO dissolution of drug powders, a 10-fold dilution, and yttrium as an internal standard at 0.1 µg/mL.

Instrumentation Used

• Shimadzu ICPE-9000 ICP-AES
• RF power: 1.3 kW; Plasma gas flow: 18 L/min; Auxiliary gas: 1.4 L/min; Carrier gas: 0.7 L/min
• Coaxial nebulizer with Scott double-tube spray chamber
• Vacuum spectrometer and echelle diffraction grating with CCD
• Axial and radial observation modes

Key Results and Discussion

Detection limits (3σ) for all 14 metals were at least tenfold below EMEA oral exposure limits (e.g., 0.0007–0.03 µg/mL). Spike recovery of tosufloxacin samples ranged between 98 % and 101 %. Two-hour continuous stability tests showed RSD < 1 % for each element. Three-day reproducibility using fresh calibrations each day yielded RSD ≈ 1 %. Analysis of real drug substances (tosufloxacin, benazepril, captopril) confirmed low-level detection and method robustness.

Benefits and Practical Applications

• Simultaneous multi-element screening with post-run addition of wavelengths and elements
• Qualitative and quantitative data retrieval from stored spectra
• Diagnostic assistant for automatic wavelength selection in the event of spectral interference
• No oxygen purge required for organic solvents, reducing complexity and cost
• Vacuum optical system enhances stability and lowers operating expenses
• Automated axial/radial switching optimizes sensitivity across diverse elements

Future Trends and Opportunities

Increased regulatory focus on trace metal impurities will drive wider adoption of ICP-AES and native ICP-MS coupling. Advances in automation, data analytics and green sample preparation are expected to streamline workflows. Integration with online dissolution and biorelevant testing may extend applications in drug development and QA/QC.

Conclusion

The ICP-AES method using Shimadzu ICPE-9000 provides a fast, reliable and cost-efficient solution for quantifying residual catalysts in pharmaceuticals. Its high sensitivity, multi-element capability and advanced data processing tools support regulatory compliance and quality assurance.

References

1. Ministry of Health, Labour and Welfare, Japan: Revised Guidelines on Impurities in New Drug Substances (2002).
2. EMEA CHMP: Specification Limits for Residues of Metal Catalysts or Metal Reagents (2008).
3. USP Ad Hoc Advisory Panel on Inorganic Impurities: Pharmacopeial Forum 34(5), 1345–1348 (2008).
4. ICH Q3C(R3): Guideline for Residual Solvents (Step 4 version).