Fast Separations of Counter Ion in an Allergy Drug Tablet Using High-Pressure Capillary IC

Importance of the Topic

Many pharmaceutical compounds are administered in their salt forms to enhance water solubility, bioavailability, and chemical stability. Accurate determination of counter ions in drug products is essential to verify the correct stoichiometry, ensure dosage accuracy, and detect potential impurities. Advanced capillary ion chromatography (IC) solutions with high pressure capability enable faster analysis with minimal resource consumption, supporting quality control and regulatory compliance in pharmaceutical environments.

Objectives and Study Overview

This study demonstrates a rapid approach for separating and quantifying the chloride counter ion in an over-the-counter allergy tablet. Using high-pressure capillary IC, the aim was to reduce analysis time while maintaining high resolution and sensitivity, optimizing conditions for routine pharmaceutical testing.

Used Instrumentation

• Thermo Scientific Dionex ICS-5000+ HPIC capillary IC system (up to 5000 psi)
• IonSwift MAX 200 capillary monolith anion-exchange column (0.25 × 250 mm)
• Capillary EGC-KOH eluent generator cartridge
• Dionex CR-ATC Trap Column and CRD 200 Carbonate Removal Device
• ACES 300 Capillary Electrolytic Suppressor
• Dionex AS-AP Autosampler and Chromeleon CDS

Methodology and Instrumentation

• Sample Preparation: A 60 mg tablet was pulverized, extracted in 20 mL deionized water at 80 °C for 30 min, cooled, filtered (0.45 µm), and diluted 1:10.
• Injection Volume: 0.4 µL.
• Eluent: KOH gradient (2–50 mM) generated electrolytically.
• Flow Rates: 10, 20, and 25 µL/min at 30 °C column temperature.
• Detection: Suppressed conductivity (ACES 300, CRD 200), current stepped from 8 to 18 mA.
• Backpressure: 1,900–4,500 psi across flow conditions.

Key Results and Discussion

• Calibration: Seven-anion standard dilution yielded linearity (r2 > 0.999) for chloride and other inorganic anions.
• Speed: Increasing flow from 10 to 25 µL/min reduced chloride retention from ~7 min to ~2.5 min.
• Resource Efficiency: Daily water consumption of 30–40 mL and minimal sample volume (0.4 µL) support sustainable operation.
• Sensitivity: Comparable mass detection limits to standard-bore IC due to enhanced signal and low system noise.

Benefits and Practical Application of the Method

• High throughput analysis for routine QA/QC labs.
• Reduced waste generation and lower consumable costs.
• Extended lifetime of eluent generator cartridges.
• Always-ready operation with rapid equilibration and low carryover.

Future Trends and Opportunities

Advances in capillary IC are expected to focus on further miniaturization, integration with mass spectrometry, and enhanced monolith column chemistries. Automation of sample preparation and multiplexing of capillary systems will drive productivity in pharmaceutical and environmental testing. Continuous development of low-dead-volume interfaces and improved suppressor designs will support even faster separations and broader analyte coverage.

Conclusion

High-pressure capillary IC using the Dionex ICS-5000+ HPIC system and IonSwift MAX 200 column enables rapid, sensitive, and resource-efficient separation of pharmaceutical counter ions. By optimizing flow rate and temperature, chloride analysis time in an allergy tablet is reduced by over 60%, demonstrating a powerful tool for modern pharmaceutical analytics.

Reference

1. Thermo Fisher Scientific. Dionex Technical Note 113, Practical Guidance for Capillary IC, Sunnyvale, CA, 2012.
2. Thermo Fisher Scientific. Dionex ICS-5000 Installation Manual, Doc No. 065343, Sunnyvale, CA, 2011.
3. Thermo Fisher Scientific. Dionex Product Manual for CES 300 Suppressors, Doc No. 065386, Sunnyvale, CA, 2010.
4. Thermo Fisher Scientific. Dionex AS-AP Operator’s Manual, Doc No. 065361, Sunnyvale, CA, 2012.
5. Christison T., Pang F., Lopez L. Fast Separations of Counter Ion in an Allergy Drug Tablet Using High-Pressure Capillary IC, Thermo Fisher Scientific Technical Note 120, Sunnyvale, CA, 2016.