Residual ethylene oxide (EtO) is a toxic and carcinogenic impurity in multiple commonly used pharmaceutical excipients such as polysorbate, polyethylene glycol (PEG), and polyethylene oxide (PEO). Limits on the presence of EtO in pharmaceutical products are in place, and it is routinely measured using USP chapter <228>, Ethylene Oxide and Dioxane. Real-time mass spectrometry provides an attractive option for rapid testing of consumer and pharmaceutical products for these and similar volatile organic compounds (VOCs). An alternative method for quantitation of residual EtO is in development using SIFT-MS which provides real-time results.

This eChalk Talk discusses an alternative method in development for the quantitation of residual EtO using SIFT-MS which provides real-time results. This method takes a typically two-day protocol for sample preparation and analysis and provides the same quantitative result in under two hours, including blanks and system suitability solutions. It uses a small fraction of the amount traditionally required and reduces or eliminates concerns about chromatographic resolution and sensitivity associated with proposed revisions to USP Chapter <621>, Chromatography. Experiments are ongoing to validate this procedure as an alternative method for USP <228> and related PEG, PEO, and polysorbate monographs.

K. Chad Bastian, Ph.D.

Chad Bastian is a Principal Scientist at Alcami Corp., a pharmaceutical contract development and manufacturing organization headquartered in North Carolina. He has over 20 years of experience using liquid and gas chromatography coupled with mass spectrometry to support pre-clinical development of small molecules and biologicals, including characterization, impurity identification, release and stability studies, and extractable and leachable testing. Prior to working in industry, Chad worked as a post-doctoral researcher with the Water Resources Division of the USGS (Lawrence, Kansas) after obtaining his Ph.D. in civil/environmental engineering at Purdue University (West Lafayette, Indiana).