Novel strategy for multi-critical quality attributes analysis of pharmaceutical excipient polyethylene glycol by...

Polyethylene glycol (PEG) is one kind of polymeric pharmaceutical excipient widely used in pharmaceutics. The critical quality attributes (CQAs) are essential to their physicochemical properties and functions. However, there is no effective strategy to rapidly and simply analyze PEG multi-CQAs. Herein, a novel strategy was developed to simultaneously evaluate four PEG CQAs including average degree of polymerization, average molecular weight, weight-average molecular weight and polydispersity based on comprehensive identification and mathematical models of PEG components. In this strategy, an ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was established and different types and concentrations of mobile phase additives were optimized to overcome the mass discrimination effect of PEG components. MS data was deconvoluted by molecular feature extraction to identify PEG components with multi-charged quasimolecular ions. A total of 168 PEG components were identified in PEG mixture samples. Mathematical models were established based on the logarithmic relation between the degree of polymerization and retention time and a theoretical database including 220 detected and predicted PEG components was constructed to rapidly recognize and identify PEG components in PEG excipients and preparations samples. The calculation formulae for multi-CQAs using UHPLC-Q-TOF/MS analysis results were created, then the strategy workflow to evaluate multi-CQAs was established and validated by PEG standards, showing high efficiency for quality control of PEG excipients and their preparations.