A fast HPAE-PAD method for determination of carbohydrates and glycols in pharmaceutical formulations

Significance of the Topic

Analytical control of inactive carbohydrate and glycol excipients is critical for quality and safety of pharmaceutical formulations. These compounds may cause digestive intolerance in sensitive populations and require accurate quantification to meet regulatory standards and ensure product consistency.

Aims and Overview of the Study

The study aims to develop a rapid and sensitive high performance anion exchange chromatography method with pulsed amperometric detection for six common carbohydrates and glycols in over-the-counter formulations. It introduces an optimized protocol using a Thermo Scientific CarboPac PA300 column with electrolytic eluent generation to improve speed and reproducibility over existing approaches.

Methodology and Instrumentation

Key elements of the assay include:

• Column and system: Thermo Scientific Integrion HPIC system equipped with CarboPac PA300 analytical (2×250 mm) and guard (2×50 mm) columns
• Eluent: electrolytically generated 22 mM KOH, isocratic at 0.275 mL/min
• Detection: gold pulsed amperometric detector with optimized potential waveform
• Temperature control: column at 30 °C, sample tray at 4 °C
• Sample preparation: 20 000-fold dilution of formulations before analysis

Results and Discussion

The method achieved baseline separation of propylene glycol, sorbitol, mannitol, maltitol, glucose and sucrose within 16.8 minutes with resolution factors between 2.9 and 18.5. Calibration was linear over 2–33.3 mg/L for all analytes with correlation coefficients exceeding 0.99. Retention time RSD was below 0.3% and peak area RSD below 2% across three concentration levels. Detection limits corresponded to a signal-to-noise ratio of 10:1 at or below 1 mg/L. Recovery experiments in three pharmaceutical formulations yielded 87–108% for all targets. Robustness testing with ±10% variations in flow, eluent concentration and temperature showed negligible impact on retention, resolution and peak shape.

Benefits and Practical Applications

This method offers:

• Direct analysis without derivatization, reducing labor and hazardous reagents
• High throughput with short run time and automated eluent generation
• High sensitivity and selectivity for nonchromophoric carbohydrates and glycols
• Applicability to quality control of over-the-counter formulations and FODMAP content screening

Future Trends and Possibilities

Further developments may include separation of additional glycol excipients such as glycerol using alternative stationary phases, integration with mass spectrometry for structural analysis, and miniaturized systems for higher throughput and reduced solvent consumption.

Conclusion

The presented HPAE-PAD assay using a CarboPac PA300 column and electrolytic eluent generation provides a robust, rapid and sensitive tool for quantifying key carbohydrates and glycols in pharmaceutical formulations. Its high precision, accuracy, and automation potential make it suitable for routine quality control and formulation development.

References

1. U.S. Food and Drug Administration. 21 CFR Part 210 and 211. Definitions and Quality Control Requirements.
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4. Rocklin RD. J Chromatogr. 1991;546:175–187.
5. Thermo Fisher Scientific Application Note 117. Quantification of Carbohydrates and Glycols in Pharmaceuticals.