In Support of FDA Guidance for Industry: Measurement of Ethylene Glycol and Diethylene Glycol in Alcohol Ethoxylates by flow modulated GCxGC

The recent guidance published by the FDA highlighting the need to ensure the detection of diethylene glycol (DEG) and ethylene glycol (EG) in pharmaceutical products, drugs and excipients (i.e. co-ingredients within drugs) led to a development of a method for their quantitation in alcohol ethoxylates. This came out of multiple reports in the recent past of fatal poisonings, many involving children, who ingested drug products manufactured with DEG- or EG-contaminated components. The maximum level of DEG+EG in such products, as specified by the FDA guidance, is 0.1 wt%. Flow modulated GCxGC was used to measure DEG and EG in alcohol ethoxylates. The method allows for precise measurements and has the advantage of increased resolution and separation power especially in the case where overlapping peaks are present. The GCxGC method affords quantitation levels (LOQ) of 0.008 wt%. Samples of the different commercial products are analyzed and include ethoxylates based on the C1213-, C1215-, C1415- and C911-hydrophobes.  Samples obtained from commercial units show that the levels of DEG and EG are roughly constant across products showing that the batch-to-batch process condition variability is minimal.
The commercial alcohol ethoxylates described above contain DEG at levels of less than 0.02 wt% and EG on the order of < 0.01 wt% and meets the specification for maximum DEG+EG.