Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates.

Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates.
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泰勒分散分析与动态光散射相比,用于治疗性肽和蛋白质及其聚集体的尺寸分析。

DOI:
10.1007/s11095-011-0460-3
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发表时间:
2011-09
影响因子:
3.7
通讯作者:
Forbes, Robert T.
Forbes, Robert T.
中科院分区:
医学3区
文献类型:
--
作者:
Hawe, Andrea;Hulse, Wendy L.;Jiskoot, Wim;Forbes, Robert T.

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评价泰勒色散分析(TDA)作为测定非强制降解和强制降解制剂中治疗性肽和蛋白质流体动力学半径的新方法,并将其与动态光散射(DLS)进行比较。催产素,牛血清白蛋白,各种单克隆抗体(IgG型)和依那西普在0.05和50 mg/ml之间的浓度的流体动力学半径测定TDA和DLS。对IgG和依那西普进行强制降解(高温),并通过TDA、DLS和HP-SEC进行分析。在约0.5至50 mg/ml的浓度范围内,TDA和DLS在大小测定非应激肽和蛋白质方面是相当的。TDA甚至在较低浓度下也表现良好,其中DLS倾向于提供理论上高的Z-平均半径值。然而,由于检测物理学的差异,DLS比TDA更倾向于检测强制降解制剂中的聚集体。有利的是,TDA还能够确定小肽催产素的大小,这通过DLS是不可行的。TDA允许在宽浓度范围内准确测定肽和蛋白质的流体动力学半径,样品中存在的辅料几乎不干扰。在检测强制降解蛋白样品的分子量增加方面,其灵敏度略低于DLS。
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). The hydrodynamic radius of oxytocin, bovine serum albumin, various monoclonal antibodies (type IgG) and etanercept at concentrations between 0.05 and 50 mg/ml was determined by TDA and DLS. IgGs and etanercept were stressed (elevated temperatures) and analyzed by TDA, DLS and HP-SEC. TDA and DLS were comparable in sizing non-stressed peptides and proteins in a concentration range of about 0.5 to 50 mg/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. 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.
DOI: 10.1021/ac048846z
发表时间: 2005-02-01
影响因子: 7.4
作者:
Sharma, U;Gleason, NJ;Carbeck, JD
通讯作者: Carbeck, JD
DOI: 10.1002/jps.20347
发表时间: 2005-09-01
影响因子: 3.8
作者:
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DOI: 10.1208/aapsj080365
发表时间: 2006-01-01
期刊: AAPS JOURNAL
影响因子: 4.5
作者:
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通讯作者: Philo, John S.
DOI: 10.1098/rspa.1956.0065
发表时间: 1956-01-01
影响因子: --
作者:
ARIS, R
通讯作者: ARIS, R