Determination of Ethylene Oxide and Dioxane in Different Grades (Chain Lengths) of Polyethylene Glycols by a Single Headspace Capillary Gas Chromatography Method

Polyethylene glycols (PEGs) are widely used in the pharmaceutical industry as excipients in finished drug products. Ethylene oxide and dioxane are residual solvents in bulk PEG samples. In current USP and EP headspace gas chromatographic (HSGC) methods, ethylene oxide coelutes with other impurities in PEGs. Due to this, there is a risk of generating false out of specification (OOS) results during release testing of PEGs that could potentially lead to the rejection of good PEG batches. Therefore, a new single headspace capillary gas chromatography method was developed, which can adequately separate all peaks of interest and accurately quantitate and identify ethylene oxide and dioxane in bulk lots of various grades (different chain lengths) of polyethylene glycols (PEGs). The HSGC analysis was carried out using an Agilent DB-624 column as the primary column (60 m x 0.53 mm diameter, film thickness 3.00 µm) with stationary phase consisting of 6% cyanopropylphenyl and 94% polydimethylsiloxane. An alternate column from Thermo Scientific (TG-624) was demonstrated as an equivalent column (60 m x 0.53 mm diameter, film thickness 3.00 µm, stationary phase of 6% cyanopropylphenyl and 94% polydimethylsiloxane). HSGC analysis of PEG samples were conducted through a thermal gradient elution from 36 oC to 240 oC, and the analytes were detected by a flame ionization detector (FID). Helium was used as the carrier gas of the new HSGC method with a flow rate of 4.5 mL/min under constant flow mode. The total run time of the new method is much shorter (about 18 minutes) compared to the USP and EP methods. The new HSGC method was successfully validated according to current ICH/VICH guidelines and was found to be specific, linear, accurate, precise, robust and sensitive. An advantage of the new HSGC method is that it is suitable for routine analysis of ethylene oxide and dioxane in bulk batches of PEGs in quality control (QC) laboratories.