Ion chromatography – the all-rounder for pharmaceutical analysis

Importance of the Topic

Ion chromatography has emerged as a versatile and highly precise analytical technique in pharmaceutical analysis. It plays a critical role in ensuring drug safety and efficacy by providing reliable data on the identity, concentration, purity and stability of pharmaceutical formulations, active pharmaceutical ingredients and impurities. Its compliance with major pharmacopeias and ability to handle complex matrices with minimal sample preparation make it indispensable in quality control, formulation development and regulatory testing.

Study Objectives and Overview

The reviewed application notes illustrate how ion chromatography is applied across multiple stages of pharmaceutical production and analysis, including:

• Quantification of electrolytes and buffers in infusion and dialysis solutions
• Determination of active antibiotic compounds and their analogues
• Trace analysis of synthesis-related impurities in APIs
• Radiochemical purity assessment of PET tracers such as fluorodeoxyglucose

Each case study emphasizes rapid separation, inline sample cleanup and compliance with USP and European Pharmacopeia guidelines.

Methodology and Instrumentation

The analytical approach relies on suppressed conductivity and pulsed amperometric (PAD) detection, combined with inline sample preparation modules. Key elements include:

• Anion and cation exchange columns (eg Metrosep A Supp and Carb series) for selective separation
• Eluent systems with Na2CO3/NaHCO3 gradients or NaOH for different analytes
• Matrix suppression and inline elimination to remove high-salt backgrounds
• Preconcentration modules to reach trace detection limits in µg per liter range
• Post-column addition of alkali for sensitive PAD of aminoglycoside antibiotics

Main Results and Discussion

Pharmaceutical solutions: Rapid baseline separation of acetate, citrate, chloride and other electrolytes in hemodialysis and infusion matrices was achieved in under 20 minutes with detection limits below 0.1 mmol per liter. Inline suppression minimized sample cleanup steps.

APIs and antibiotics: Gentamicin analogues and related antibiotics were fully resolved on reversed phase columns with post-column NaOH and PAD, allowing quantification of each component in complex mixtures. Beta cyclodextrin and ephedrine derivatives were similarly characterized.

Impurities: Trace-level azide, amines, sulfate esters and metal ions in antihypertensive and other APIs were detected at µg per liter concentrations. Inline matrix elimination and preconcentration ensured high sensitivity.

Radiopharmaceuticals: [18F]FDG and its major impurity chlorodeoxyglucose were separated on anion exchange columns and monitored by PAD, confirming radiochemical purity above pharmacopeial thresholds.

Benefits and Practical Applications of the Method

Ion chromatography offers:

• High throughput and short run times for routine quality control
• Low sample preparation through inline suppression and elimination
• Trace-level detection suitable for impurity profiling
• Compliance with USP and European Pharmacopeia standards
• Flexibility to analyze inorganic ions, organic acids, antibiotics and radiochemicals

Future Trends and Opportunities

Advances in column technology, detector sensitivity and automated inline sample preparation are expected to further reduce analysis times and detection limits. Integration with mass spectrometry may expand capabilities for structural identification of unknown impurities. Radio-IC applications will grow alongside PET tracer development, enabling rapid purity checks of emerging radiopharmaceuticals.

Conclusion

Ion chromatography stands out as an all-round analytical tool in pharmaceutical laboratories. Its robust separation power, minimal sample handling and compliance with regulatory requirements make it ideal for comprehensive quality control of solutions, APIs, impurities and radiochemicals. Continuous improvements in instrumentation and methodology will extend its applicability and efficiency in drug development and manufacturing.

References

1. Ion chromatography – the all-rounder in pharmaceutical analysis WP-019EN Metrohm Herisau Switzerland 2017 page 6
2. Pharmaceutical analysis 8.000.5139EN Metrohm Herisau Switzerland 2015 page 28