caa a22 4500 445312114 CHVBK 20180317142633.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s11095-011-0460-3 doi (NATIONALLICENCE)springer-10.1007/s11095-011-0460-3 Taylor Dispersion Analysis Compared to Dynamic Light Scattering for the Size Analysis of Therapeutic Peptides and Proteins and Their Aggregates [Elektronische Daten] [Andrea Hawe, Wendy Hulse, Wim Jiskoot, Robert Forbes] ABSTRACT: Purpose: To evaluate Taylor dispersion analysis (TDA) as a novel method for determination of hydrodynamic radius of therapeutic peptides and proteins in non-stressed and stressed formulations and to compare it with dynamic light scattering (DLS). Methods: The hydrodynamic radius of oxytocin, bovine serum albumin, various monoclonal antibodies (type IgG) and etanercept at concentrations between 0.05 and 50mg/ml was determined by TDA and DLS. IgGs and etanercept were stressed (elevated temperatures) and analyzed by TDA, DLS and HP-SEC. Results: TDA and DLS were comparable in sizing non-stressed peptides and proteins in a concentration range of about 0.5 to 50mg/ml. TDA performed well even at lower concentrations, where DLS tends to provide theoretically high values of the Z-average radius. However, because of differences in the detection physics, DLS was more weighted towards the detection of aggregates in stressed formulations than TDA. Advantageously, TDA was also able to size the small peptide oxytocin, which was not feasible by DLS. Conclusion: TDA allows the accurate determination of the hydrodynamic radius of peptides and proteins over a wide concentration range, with little interference from excipients present in the sample. It is marginally less sensitive than DLS in detecting size increase for stressed protein samples. The Author(s), 2011 dynamic light scattering nationallicence hydrodynamic size nationallicence protein aggregation nationallicence protein characterization nationallicence Taylor dispersion analysis nationallicence Hawe Andrea Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box9502, 2300 RA, Leiden, The Netherlands aut Hulse Wendy PI Research Focus Group, School of Pharmacy, University of Bradford, BD7 1DP, Bradford, UK aut Jiskoot Wim Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box9502, 2300 RA, Leiden, The Netherlands aut Forbes Robert PI Research Focus Group, School of Pharmacy, University of Bradford, BD7 1DP, Bradford, UK aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2302-2310 0724-8741 28:9<2302 2011 28 11095 https://doi.org/10.1007/s11095-011-0460-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0460-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hawe Andrea Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box9502, 2300 RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Hulse Wendy PI Research Focus Group, School of Pharmacy, University of Bradford, BD7 1DP, Bradford, UK aut NATIONALLICENCE 700 1- Jiskoot Wim Division of Drug Delivery Technology Leiden/Amsterdam Center for Drug Research, Leiden University, P.O. Box9502, 2300 RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Forbes Robert PI Research Focus Group, School of Pharmacy, University of Bradford, BD7 1DP, Bradford, UK aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/9(2011-09-01), 2302-2310 0724-8741 28:9<2302 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer