Validated GC-MS methods to detect ethylene, diethylene, and triethylene glycol in serum, plasma, and urine samples

While Polyethylene glycol 3350 (PEG 3350) is approved by the USFDA for short term use by adults, it is commonly recommended for use in constipated children. Multiple reports of adverse events in children taking PEG 3350 raised safety concerns suggesting that low molecular weight species of PEG 3350 might be absorbed from the gut and cause side effects such as ethylene glycol (EG), diethylene glycol (DEG), and triethylene glycol (TEG). This article documents the development, validation, and application of analytical methods using GC-MS and GC-MS/MS for the quantitation of EG, DEG, and TEG in human plasma, serum, and urine. The analytical range for EG, DEG, and TEG was 2–20 µg/mL. The sample preparation process involves derivatization using N,O-bis(trimethylsilyl) trifluoroacetamide with 1% trimethylchlorosilane in each biological matrices. Deuterated internal standards for each of the analytes were included to provide accurate quantitation of the glycol analytes. The validated methods were applied to analyze samples a pilot study of children taking PEG 3350. DEG and TEG were detected at levels below the limit of quantitation. In summary, a platform of analytical methods was developed to evaluate glycol analogs in urine, serum, and plasma clinical samples. This study looks at the safety of Polyethylene Glycol 3350 (PEG 3350), a commonly used medication to treat constipation in adults and children. Though PEG 3350 is approved by the USFDA for short-term use in adults, concerns have arisen regarding its safety in children, particularly because PEG 3350 may break down into smaller substances that could be absorbed into the body and cause harm. These smaller substances, like ethylene glycol (EG), diethylene glycol (DEG), and triethylene glycol (TEG), were the focus of this research work. The researchers developed and tested new methods to measure these substances in blood and urine using advanced laboratory techniques called GC-MS and GC-MS/MS. They found that these substances could be detected in very small amounts, with a specific range of measurement between 2 µg/mL and 20 µg/mL. They used a special process to prepare the samples and included internal standards to ensure the results were accurate. In a pilot study involving children taking PEG 3350, the levels of DEG and TEG were found to be very low, below the detectable threshold. Overall, this study developed effective ways to test for these potentially harmful substances in clinical samples, which could help better understand the safety of PEG 3350 in children.