IC: The all-rounder in pharmaceutical analysis

Importance of Topic

Ion chromatography (IC) plays a critical role in pharmaceutical analysis by offering high sensitivity, selectivity and the ability to detect inorganic and organic ions across a wide concentration range. Regulatory frameworks such as the United States Pharmacopeia and European Pharmacopoeia require reliable, precise methods for assessing drug purity, impurities and formulation components. IC’s flexibility in column chemistry, eluent systems and detection modes makes it an ideal tool for ensuring patient safety and product quality.

Objectives and Study Overview

This white paper provides an overview of recent trends and practical applications of IC in the pharmaceutical industry. Key objectives include illustrating the use of IC for analyzing pharmaceutical solutions (e.g. haemodialysis fluids), active pharmaceutical ingredients (APIs), impurities in final products and radiochemical purity of PET tracers. Representative case studies highlight automated sample preparation, inline matrix elimination and coupling to advanced detectors.

Methodology and Instrumentation

IC workflows combine tailored separation columns, optimised eluent gradients and a range of detection methods. Major detection modes include:

• Conductivity detection (with and without chemical suppression)
• Electrochemical detection (amperometric)
• Spectrophotometric detection (UV–Vis, with optional post-column derivatisation)
• Coupled detection: IC–MS and IC–ICP-MS
• Radioactivity detection for radiopharmaceutical purity (Radio IC)

Automation advances, such as inline dilution, inline matrix elimination and sequential suppression, reduce manual intervention and improve reproducibility.

Used Instrumentation

• Ion chromatographs with automated inline sample preparation
• Columns: anion suppressor columns (e.g. Metrosep A Supp 7, 10), cation columns (e.g. Metrosep C 4)
• Conductivity detectors with sequential suppression
• Amperometric detectors for aminoglycosides
• Radioactivity detectors housed in lead-shielded enclosures for PET tracer quality control

Main Results and Discussion

Case studies demonstrate:

• Simultaneous determination of citrate, acetate and chloride in haemodialysis solutions with high precision and physiological relevance to prevent osmotic imbalance.
• Automated analysis of haemodialysis cations (Na+, K+, Ca2+, Mg2+) using non-suppressed conductivity.
• Separation and quantitation of complex API mixtures such as gentamicin constituents by pulsed amperometric detection, meeting pharmacopeial requirements.
• Trace-level detection of toxic impurities (e.g. azide in irbesartan) using inline matrix elimination, achieving recovery >100 % and RSD <2 %.
• Radio IC for assessing radiochemical purity of [18F]-labelled PET tracers, ensuring elimination of free radionuclide and minimizing patient dose.

Benefits and Practical Applications

IC offers multiple advantages in pharmaceutical quality control:

• High throughput: simultaneous multi-ion analysis in a single run.
• Wide dynamic range: from ng/L to percent levels.
• Minimal sample preparation: inline dilution and matrix removal.
• Regulatory compliance: meets USP/Ph. Eur. precision, accuracy and detection limit criteria.
• Versatility: applicable to APIs, excipients, formulation media and radiotracers.

Future Trends and Applications

Emerging developments are focused on:

• Enhanced automation and microfluidic IC for rapid, high-throughput screening.
• Integration with high-resolution mass spectrometry for comprehensive impurity profiling.
• Green chromatography: reduced organic solvent usage and ion-exchange resins with improved longevity.
• AI-driven method development for faster optimisation of separation and detection conditions.
• Portable and field-deployable IC systems for on-site pharmaceutical manufacturing monitoring.

Conclusion

Ion chromatography has established itself as a versatile, robust and regulation-compliant technique for comprehensive pharmaceutical analysis. Its adaptability to diverse matrices, combined with advanced detection and automation strategies, ensures reliable quality control of drugs, excipients and radiopharmaceuticals. Ongoing innovations in instrumentation and method development will further enhance its role in safeguarding drug safety and efficacy.

Reference

• Metrohm White Paper “IC: The all-rounder in pharmaceutical analysis”, WP-019EN, February 2017