Detection and quantification of leached ethylene glycol in biopharmaceuticals by RP-UHPLC.

ABSTRACT

Biopharmaceuticals are in direct contact with different plastic materials, which can contribute to process-related impurities. Polyethylene terephthalate glycol (PETG) is used for storage and transportation of biopharmaceuticals and it is synthetized from the poly-condensation reaction between ethylene glycol, 1,4-cyclodimethanol and dimethyl terephthalate. PETG bottles are analyzed for such impurities prior to release; however, the nature of the pharmaceutical matrix can extract impurities, so it is important to measure these contaminants in biopharmaceuticals. This study shows a liquid chromatography method for the quantification of ethylene glycol in PETG materials as an alternative to the standard USP colorimetric method. The method is based on the derivatization of ethylene glycol with benzoyl chloride in a Schotten-Baumann reaction. We present a comprehensive method development and validation. The method allows the detection and quantification of leached and extracted ethylene glycol directly in biopharmaceuticals after years of storage in contact with PETG bottles. Results showed residual ethylene glycol in drug substances to a level of ≈  0.1-0.5 µg/mL exposed during 2-6 years of storage in PETG bottles and ≈ 0.2-0.9 µg/mL in biopharmaceuticals. Graphical abstract Biopharmaceuticals must be free or low concentration for leachables, FR-UHPLC-UV analysis is a precise and accurate analytical method for ethylene glycol measurement. This leachable is commonly present in products in direct contact with PETG plastic.