Determination of Inorganic Counterions in Pharmaceutical Drugs Using Capillary IC

Significance of the Topic

Counterion analysis in pharmaceutical salts is essential for ensuring drug performance, stability, and regulatory compliance. By accurately quantifying inorganic counterions, ion chromatography supports formulation optimization and quality control workflows.

Study Objectives and Overview

This work evaluates capillary ion chromatography with suppressed conductivity detection for determining inorganic anions and cations in two drug products: a type 2 diabetes medication (chloride) and a cholesterol control formulation (calcium, sodium, magnesium). The goal is to demonstrate fast, reliable analysis with minimal reagent consumption and system downtime.

Methodology

Samples were prepared by dissolving tablets in water at 50 °C, treatment with OnGuard RP cartridges, filtration (0.4 µm), and 1:10 dilution. Anionic analysis employed a Dionex IonPac AS19 capillary column (0.4×250 mm) with 40 mM KOH eluent (generated by EGC-KOH), 10 µL/min flow, 0.4 µL injection, 30 °C column temperature, and ACES 300 suppressor. Cationic analysis used a Dionex IonPac CS12A capillary column under a 20 mM MSA gradient, identical flow, injection, and temperature settings, and a CCES 300 suppressor.

Instrumentation Used

• Thermo Scientific Dionex Capillary ICS-5000 RFIC system
• Dionex AS-AP Autosampler
• IonPac AS19 and CS12A capillary columns (0.4×250 mm)
• ACES 300 and CCES 300 suppressors
• Dionex EGC-KOH and EGC-MSA eluent generators
• Chromeleon Chromatography Data System

Main Results and Discussion

Anion analysis yielded a chloride concentration of 16.6 mg/L, equivalent to 0.453 mg per tablet, in under 5 minutes with clear peak resolution. Cation analysis separated sodium (0.147 mg/L, 1.13 µg/tablet), magnesium (0.705 mg/L, 5.47 µg/tablet), and calcium (3.59 mg/L, 27.8 µg/tablet) effectively from excipients.

Practical Applications and Benefits

Capillary RFIC systems reduce eluent and waste production, enable continuous operation with extended cartridge life (up to 18 months), and minimize calibration frequency. Fast run times and small injection volumes streamline QC and salt selection processes in pharmaceutical development.

Future Trends and Potential Applications

Advances may include integration with mass spectrometry detection, automated on-line sampling, further miniaturization for microfluidic devices, and implementation in continuous manufacturing and green analytical protocols.

Conclusion

Capillary ion chromatography with suppressed conductivity detection offers a rapid, sensitive, and resource-efficient approach for quantifying inorganic counterions in pharmaceutical formulations, supporting robust QC and formulation development.

Reference

1. Dionex Corporation (Thermo Scientific), Quantification of Anions in Pharmaceuticals, Application Note 116, LPN 0924, 2007.
2. Dionex Corporation (Thermo Scientific), Determination of Sulfate Counter Ion and Anionic Impurities in Aminoglycoside Drug Substances by IC with Suppressed Conductivity Detection, Application Note 190, LPN 1946, 2007.
3. Wermuth CG, Stahl PH. Handbook of Pharmaceutical Salts: Properties, Selection and Use; Wiley-VCH: Weinheim, Germany, 2002; pp. 1–7.
4. Berge SM, Bighley LM, Monkhouse DC. Pharmaceutical Salts. J. Pharm. Sci. 1977;66(1):1–19.