Towards improved characterisation of complex polyethylene glycol excipients using supercritical fluid chromatography-evaporative light scattering detection-mass spectrometry and comparison with size exclusion chromatography-triple detection array

• Published in: Journal of Chromatography A 2021-02, Vol.1638, p.461839, Article 461839
• Main Authors: Poulton, Andrew M, Poulten, Rebecca C, Baldaccini, Alice, Gabet, Anaëlle, Mott, Rebecca, Treacher, Kevin E, Roddy, Emily, Ferguson, Paul
• Format: Article
• Language: English
• Subjects: Dispersity; Evaporative light scattering; Polyethylene glycol; Polymer analysis; Size exclusion chromatography; Supercritical fluid chromatography
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2020.461839

•Polyethylene glycol 2000 oligomers are easily and fully resolved with SFC-ELSD-MS.•Differentiation of PEG ends groups observed and followed the expected elution order.•Unlike SEC, unusual bimodal distribution of PEG- OCH2COOH quickly and easily seen.•Dispersity determination comparative to size exclusion chromatography.•Potential for much simpler calibration-less polymer dispersity determination. The application of supercritical fluid chromatography (SFC) coupled to an evaporative light scattering detector (ELSD) and mass spectrometer (MS) was evaluated for the characterisation of three analogues of functionalised polyethylene glycol (PEG) 2000 (m-PEG-OH, m-PEG-cm and cm-PEG-cm (where m = OCH3 and cm = OCH2COOH)). These polymers are common excipients in drug product formulations for pharmaceuticals as they help provide the desired pharmacokinetic profile for successful drug delivery. A SFC-ELSD-MS method was developed which was selective to all three polymers, and allowed visualisation of these low UV chromophore materials. The method provided baseline resolution of the individual oligomers which allowed facile calculation of the polymer dispersity. A number of molecular weight characteristics were calculated, which showed the SFC-ELSD-MS methodology to be comparable with the current standard of analysis using size exclusion chromatography (SEC) with a triple detector array (TDA). The increased resolving power of SFC compared to SEC revealed a bimodal distribution of oligomers in the cm-PEG-cm 2000 polymer, which was not observed using SEC-TDA and exemplified SFC-ELSD as an orthogonal approach for polymer characterisation with the potential for much simpler, reduced sample and instrument preparation, calibration-less dispersity determination. When combined with SEC-TDA data, this combination allows a more complete characterisation of complex formulations excipients.