Quantification of Carbohydrates and Glycols in Pharmaceuticals

Significance of the Topic

Pharmaceutical products often contain nonchromophoric compounds such as carbohydrates, sugar alcohols and glycols which must be quantified to ensure identity, strength and purity. Ion chromatography with amperometric detection enables sensitive and selective measurement of these compounds, even in complex or high-ionic strength formulations.

Objectives and Study Overview

This work compares three anion-exchange columns (Dionex IonPac ICE-AS1, CarboPac PA10 and CarboPac MA1) coupled to amperometric detection for quantification of common simple sugars, sugar alcohols and glycols in two over-the-counter medications (a cough suppressant and a multisymptom cold/flu formulation). The aim was to evaluate selectivity, detection limits, linearity, precision, accuracy and applicability to real samples.

Methodology and Instrumentation

• The system comprised a Thermo Scientific Dionex DX-500 with GP40 pump, ED40 electrochemical detector, LC30 oven and AS3500 autosampler.
• Three analytical columns were used:
  • ICE-AS1 (ion exclusion mechanism; sulfonated polystyrene/divinylbenzene)
  • CarboPac PA10 (monosaccharide-selective latex anion-exchange)
  • CarboPac MA1 (high-capacity macroporous anion-exchange)
• Eluents included perchloric acid for ICE-AS1 and sodium hydroxide at varying concentrations for PA10 and MA1, all operated isocratically.
• Detection was performed by integrated pulsed amperometry using platinum or gold electrodes, eliminating interferences from nonoxidizable matrix components.
• Sample preparation involved weight-based dilutions of the formulations (up to 1000-fold) and standard addition for recovery tests.

Main Results and Discussion

• ICE-AS1 provided rapid separation of glycols (propylene glycol, glycerol) and sugar alcohols within 10 min, but limited carbohydrate resolution.
• PA10 resolved sugar alcohols and monosaccharides isocratically, with propylene glycol and glycerol coeluting near the void volume.
• MA1 achieved baseline separation of glycols, sugar alcohols and carbohydrates in a single run, at the expense of longer analysis times.
• Method detection limits on MA1 ranged from 0.07 mg/L for glycerol to 0.7 mg/L for sucrose in a 10 µL injection, with linearity over at least three orders of magnitude (r2 ≥ 0.995) and precision (RSD 2–4% at 10 mg/L).
• Recoveries after 50 mg/L standard addition ranged from 87% to 114% for all analytes, demonstrating accuracy in real sample matrices.
• Analysis of two formulations determined active and inactive carbohydrate contents consistent with labeled ingredients and revealed trace unlabeled sugars likely as impurities.

Benefits and Practical Applications

This approach allows comprehensive profiling of nonchromophoric excipients and active ingredients in pharmaceuticals, supporting quality control and regulatory compliance. The choice of column can be tailored to target compounds, balancing analysis speed, selectivity and capacity.

Future Trends and Potential Applications

• Integration with automated sample preparation and high-throughput chromatography for routine QC environments.
• Development of mixed-mode or novel stationary phases to further reduce run times while maintaining resolution.
• Application to biologics, complex drug delivery systems and monitoring of carbohydrate-based impurities during manufacturing.

Conclusion

Anion-exchange chromatography with pulsed amperometric detection on Dionex ICE-AS1, CarboPac PA10 and MA1 columns provides versatile, sensitive and accurate quantification of glycols, sugar alcohols and carbohydrates in pharmaceutical formulations. MA1 offers the broadest separation capability, while ICE-AS1 and PA10 provide rapid analysis for specific target classes.

References

Key regulatory requirements and application notes from the US FDA and Thermo Fisher Scientific were consulted to develop and validate these methods, including CFR Title 21 guidelines and Dionex application and technical notes.