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

Poulton, Andrew M.; Poulten, Rebecca C.; Baldaccini, Alice; Gabet, Anaëlle; Mott, Rebecca; Treacher, Kevin; Roddy, Emily; Ferguson, Paul

doi:10.1016/j.chroma.2020.461839

Cited by 11 publications

(13 citation statements)

References 22 publications

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“…Analysis of such impurities is difficult owing to the similarity in properties of the impurity to the bulk materials and advanced characterization techniques are required. [205] For example, with methoxy-PEG, it is well known that diol impurities form as a result of the trace amounts of water in the polymerization. [206] Whilst for some applications this may not be problematic, if further modification of this polymer is required to create diblock copolymers then inevitably unwanted triblock copolymer impurities result and may impact on the performance of the final product.…”

Section: Control Of Impuritiesmentioning

confidence: 99%

Highway to Success—Developing Advanced Polymer Therapeutics

England

Akhtar

2021

Advanced Therapeutics

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Polymer therapeutics are advancing as an important class of drugs. Polymers have already demonstrated their value in extending the half‐life of proteins. They show great potential as delivery systems for improving the therapeutic index of drugs, via biophysical targeting and more recently with more precision targeting. They are also important for intracellular delivery of nucleic acid based drugs. The same frameworks that have been successfully applied to improve the small molecule drug development can be adopted. This approach together with improved pathophysiological disease knowledge and critical developability considerations, imperative given the size and complexity of polymer therapeutics, provides a structured framework that should improve their clinical translation and exploit their functionality and potential. Progress in understanding the right target, gaining the right tissue and cell exposure, ensuring the right safety, selecting the right patient population is discussed. The right commercial considerations are outlined and the need for a multi‐disciplinary approach is emphasized. Crucial developability factors together with scientific and technical advancements to enable pharmaceutical development of a quality robust product are addressed. It is argued that by applying this structured approach to their design and development, polymer therapeutics will continue to grow and develop as important next generation medicines.

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Section: Control Of Impuritiesmentioning

confidence: 99%

Highway to Success—Developing Advanced Polymer Therapeutics

England

Akhtar

2021

Advanced Therapeutics

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“…Most detectors for HPLC and GC can also be applied to SFC, although it is necessary to confirm that the detectors can work under high pressure conditions. Presently, UV-visible light detector (UV-VIS), mass spectrometer, 26) flame ionization detector (FID), evaporated light scattering detector (ELSD), [27][28][29] electroncapture detector (ECD), 30) corona-charged aerosol detector (CAD) 31) and electrochemical detector (ED) 32,33) have been reported to work as SFC detectors. Among these detectors, as with HPLC, UV-VIS is a standard detector for the analysis of compounds having UV absorption.…”

Section: Analytical Chemistry In Biology and Medicinementioning

confidence: 99%

Emerging Separation Techniques in Supercritical Fluid Chromatography

Yamamoto

Machida

Kotani

et al. 2021

CHEMICAL & PHARMACEUTICAL BULLETIN

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Supercritical fluid chromatography (SFC) has unique separative characteristics distinguished from those of HPLC and gas chromatography. At present, SFC is widely used and there are many applications in various biological, medical, and pharmaceutical fields. In this review, we focus on recently developed novel techniques related to SFC separation including: new column stationary phases, microfluidics, twodimensional separation, and gas-liquid separation. In addition, we discuss the application of SFC using a water-containing modifier to biological molecules such as amino acids, peptides, and small proteins that had been challenging analytes.

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“…Poulton et al. proposed the first modern packed‐column SFC‐ELSD‐MS method that separated PEGs with methoxy and acidic end groups [18]; however, the selection of the mobile phase, make‐up solvent, and the corresponding ions produced was not fully detailed.…”

Section: Introductionmentioning

confidence: 99%

“…Building on the work by Poulton et al. [18], this work sought to develop new SFC‐MS methods to characterize PEGs with different end groups. The use of MS addresses the lack of a chromophore within the PEG structures by facilitating the PEG chain detection by ionization, resulting in a reliable and robust approach that measures differences between PEG batches and supports impurity profiling [6].…”

Section: Introductionmentioning

confidence: 99%

“…Coupling LC with MS can aid polymer characterization and quantification, but the use of aerosol detectors is more prevalent in quality control environments as an alternative to UV detectors to detect polymeric materials that lack a chromophore [6,13,17]. Further, enhanced methods of analysis are still required to fully understand and control the quality of the final drug product when using these materials and ensure drug efficacy [18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Controlling the positive ion electrospray ionization of poly(ethylene glycols) when using ultra‐high‐performance supercritical fluid chromatography‐mass spectrometry

Cancho‐Gonzalez,

Ferguson,

Herniman

et al. 2023

J of Separation Science

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Poly(ethylene glycols) are complex polymers often added to pharmaceutical formulations to improve drug solubility and delivery. One of the main challenges when using chromatographic techniques coupled to mass spectrometry is the unselective ionization of poly(ethylene glycols) oligomers. Additionally, when the chain length is large enough, multiple charged species are formed, further complicating the mass spectra and processing. This study uses the advanced oligomer separation provided by supercritical fluid chromatography with a mass spectrometry approach that selectively ionizes poly(ethylene glycols) as ammoniated molecules to simplify data analysis and facilitate batch‐to‐batch comparisons. Several visual representations of the response of the ionization events based on the polymer molecular weight and the repeating unit were used to elucidate trends in ionization. Evaluation of the influence of the oligomer length and end‐group on the electrospray ionization of the polymer allowed the development of a process to enable selective ionization for these complex polymers.

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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

Cited by 11 publications

References 22 publications

Highway to Success—Developing Advanced Polymer Therapeutics

Highway to Success—Developing Advanced Polymer Therapeutics

Emerging Separation Techniques in Supercritical Fluid Chromatography

Controlling the positive ion electrospray ionization of poly(ethylene glycols) when using ultra‐high‐performance supercritical fluid chromatography‐mass spectrometry

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