Evaluation of a method for high throughput solubility determination using a multi-wavelength UV plate reader.
Evaluation of a method for high throughput solubility determination using a multi-wavelength UV plate reader.
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使用多波长 UV 读板仪进行高通量溶解度测定方法的评估。
DOI：
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发表时间：
2002
影响因子：
1.8
通讯作者：
Chegnyue Zhu
中科院分区：
文献类型：
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作者：
Teng;Hong Shen;Chegnyue Zhu
水的溶解度是一个重要的物理化学性质，必须在药物发现研究中及早解决。由于很难准确预测水在硅胶中的溶解度，因此需要高通量实验测定水的溶解度。本研究评价了一种使用多波长紫外板阅读器和一次性96孔紫外板快速测定溶解度的方法。结果表明，该方法具有灵敏度和重现性，可以有效地测定低至1微米的溶解度，在1-1000微米的范围内，用UV读数法和高效液相色谱法测定的溶解度之间有很好的相关性(R&gT；0.97)。除了出色的灵敏度和重现性外，UV平板阅读器方法还提供了在存在或不存在二甲基亚砜的情况下测定热力学溶解度的灵活性，二甲基亚砜是高通量筛选过程中组合化合物广泛使用的溶剂。
Aqueous solubility is a critical physicochemical property and must be addressed early during drug discovery research. Due to the difficulty in accurately predicting aqueous solubility in silico, high throughput experimental determination of aqueous solubility is in great demand. This study evaluates a method using a multi-wavelength UV plate reader and disposable 96-well UV plates for fast solubility determination. It was demonstrated that this method has the sensitivity and reproducibility to effectively determine solubility as low as 1 micro M. Excellent correlation (R>0.97) was observed between the solubility determined using the UV reader method and the HPLC method over the range of 1-1000 micro M for a diverse set of pharmaceutical compounds. In addition to excellent sensitivity and reproducibility, the UV plate reader method also offers the flexibility of being able to determine thermodynamic solubility in the presence or absence of dimethyl sulfoxide, which is a solvent widely used for combinatorial compounds during high throughput screening.