Development and validation of methods for the determination of ethylene glycol and diethylene glycol impurities in soft dosage forms

Introduction. A number of excipients such as propylene glycol, sorbitol and glycerol used in the manufacture of soft dosage forms can be sources of toxic impurities of ethylene glycol and diethylene glycol. The content of these impurities must be controlled for the safe use of such pharmaceuticals. The high level of toxicity of ethylene glycol and diethylene glycol, low standards of their content, as well as the variety and complexity of the composition of dosage forms require the use of highly sensitive and selective analytical techniques. Objective. Development and validation of methods for quantitative determination of ethylene glycol and diethylene glycol by gas chromatography in five samples of soft dosage forms of different composition. Material and Methods. The object of the study was five samples of soft dosage forms. The composition of these pharmaceutical preparations includes propylene glycol and various macrogol compounds. Results. Methods of quantitative determination of ethylene glycol and diethylene glycol by GC-FID method in five samples of soft dosage forms of different composition were developed. It was demonstrated that the differences in the composition of the studied objects require an individual approach to the analysis of these impurities - selection of chromatographic columns and temperature regimes, allowing to separate the analyzed components from the drug matrix. The applicability of the developed analytical methods for quantitative determination of ethylene glycol and diethylene glycol in the studied preparations was confirmed within the framework of validation experiments. Conclusion. This study demonstrated the possibility of using the GC-FID method to control the content of impurities of ethylene glycol and diethylene glycol in five soft dosage forms of different composition.