Purity Test of Sucralose, Pharmaceutical Excipients Standard 2018

Importance of Topic

Sucralose is a widely used artificial sweetener in pharmaceutical formulations. Monitoring residual methanol in sucralose is critical to ensure patient safety, meet regulatory requirements and maintain product quality.

Objectives and Study Overview

The purpose of this work was to validate an updated headspace GC method for quantifying methanol in sucralose in accordance with the 2018 Pharmaceutical Excipients Standard. Key aims included demonstrating reproducibility, accuracy and compliance with the specified methanol limit of 0.1 %.

Methodology and Instrumentation

Sample Preparation:

• Standard solution: Methanol (0.25 g) and t-butyl alcohol internal standard diluted to 100 mL, then further diluted to 250 mL (100 µg/mL methanol, 20 µg/mL internal standard); 10 mL aliquots placed in 20 mL headspace vials.
• Test solution: 1.0 g sucralose mixed with internal standard to a final internal standard concentration of 20 µg/mL in 100 mL; 10 mL aliquots placed in headspace vials.

Analytical Procedure:

• Headspace equilibration at 60 °C for 20 minutes.
• Injection into GC-FID via splitless mode (0.4 mL injection volume).
• GC oven program: 40 °C (1 min), ramp 5 °C/min to 60 °C, then 40 °C/min to 240 °C (5 min hold).
• Carrier gas: Helium at 15 mL/min.
• Detection: Flame ionization detector at 250 °C.
• Calculation: Amount of methanol (%) = (Ms/Mt) × (Qt/Qs) × (2/5), where Ms is mass of methanol in standard, Mt is mass of sucralose.

Used Instrumentation

• Gas chromatograph with FID detection
• Headspace autosampler (Alpha MOS HT2000H)
• Capillary column: InertCap 624MS (0.53 mm I.D. × 60 m, 3.00 μm film thickness)

Main Results and Discussion

Chromatograms for standard and test solutions showed clear separation of methanol and t-butyl alcohol peaks. Repeatability was assessed over six injections:

• Relative standard deviation (RSD) of the methanol/internal standard ratio in the calibration standard (Qs): 2.23 %.
• RSD of the ratio in the test sample (Qt): 1.50 %.

The calculated methanol content in sucralose was 0.0296 %, well below the 0.1 % regulatory limit, confirming the method’s suitability.

Benefits and Practical Applications

This validated headspace GC-FID method offers high sensitivity, reproducible results and compliance with updated pharmacopeial standards. It can be readily implemented in quality control laboratories for routine monitoring of residual solvents in excipients.

Future Trends and Application Possibilities

Advances may include automation of sample preparation, miniaturized headspace systems for faster throughput and coupling with mass spectrometry for simultaneous multi-solvent analysis. Integration with laboratory information management systems will enhance data traceability and regulatory reporting.

Conclusion

The revised headspace GC method reliably quantifies methanol in sucralose with excellent repeatability and sensitivity. It meets the requirements of the 2018 Pharmaceutical Excipients Standard and supports robust quality assurance in pharmaceutical excipient testing.

References

• Pharmaceutical Excipients Standard 2018. Ministry of Health, Labour and Welfare.