Abrigo Nicolas, Selaya Susan Daniela, Mohammad Adil, Shakleya Diaa, Brown Dustin G, Zhang Jinhui, Pratt Valerie, Green Jody E, Degunia Amanda, Bennett Michael, Bloom Kaitlyn, Rogers Lynnette, Khan Aiman Q, Heuckeroth Robert O, Faustino Patrick J
Office of Pharmaceutical Quality Research, Center for Drug Evaluation and Research Food and Drug Administration, Silver Spring, MD, USA.
Office of Product Quality Assessment I, Center for Drug Evaluation and Research Food and Drug Administration, Silver Spring, MD, USA.
Bioanalysis. 2025 May;17(10):651-660. doi: 10.1080/17576180.2025.2506352. Epub 2025 May 22.
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.
虽然聚乙二醇3350（PEG 3350）已获美国食品药品监督管理局批准供成人短期使用，但通常也被推荐用于便秘儿童。多项关于服用PEG 3350的儿童出现不良事件的报告引发了安全担忧，这表明PEG 3350的低分子量物质可能会从肠道吸收并引发诸如乙二醇（EG）、二甘醇（DEG）和三甘醇（TEG）等副作用。
本文记录了使用气相色谱 - 质谱联用仪（GC - MS）和气相色谱 - 串联质谱联用仪（GC - MS/MS）对人血浆、血清和尿液中的EG、DEG和TEG进行定量分析方法的开发、验证及应用。
EG、DEG和TEG的分析范围为2 - 20μg/mL。样品制备过程包括在每种生物基质中使用含1%三甲基氯硅烷的N,O - 双（三甲基硅基）三氟乙酰胺进行衍生化。每种分析物均包含氘代内标物，以提供对二醇分析物的准确定量。
经过验证的方法被应用于分析服用PEG 3350的儿童的样本。检测到的DEG和TEG水平低于定量限。总之，开发了一个分析方法平台，用于评估尿液、血清和血浆临床样本中的二醇类似物。
