CNS Chemistry Department, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, PO Box 15437, Wilmington, DE 19850-5437, USA.
J Chromatogr A. 2010 Mar 19;1217(12):1950-5. doi: 10.1016/j.chroma.2010.01.071. Epub 2010 Jan 29.
A rapid throughput octanol-water lipophilicity measurement based on 96-well shake-flask and LC/UV/APPI/MS is described. The method utilizes central liquid storage where compounds are stored as 10 mM solutions in dimethyl sulfoxide (DMSO). The DMSO is subsequently removed to generate solid like material used for LogD measurement. The removal of DMSO minimizes the concern for potential DMSO cosolvent effect on the measured value. Sample preparation is automated using a liquid handling workstation with 96-well pipetter. Both octanol and buffer phases are quantified using state of the art ultra-high pressure HPLC coupled with a superficially diffused core reversed-phase column and an atmospheric pressure photo ionization mass spectrometer. The throughput of the method is two days for a batch of 96 compounds. The method has been validated using 72 literature compounds with diverse ionization and LogD values ranging from -2 to +6. The observed coefficient of determination r(2) is 0.9973.
本文描述了一种基于 96 孔振摇瓶和 LC/UV/APPI/MS 的快速高通量辛醇-水脂溶性测量方法。该方法利用中央液体储存库，将化合物以 10mM 的 DMSO 溶液形式储存。随后除去 DMSO，生成用于 LogD 测量的固态物质。除去 DMSO 最大限度地减少了对 DMSO 共溶剂对测量值潜在影响的担忧。样品制备使用带有 96 孔移液器的液体处理工作站自动化完成。同时使用最先进的超高压 HPLC 结合表面扩散核心反相柱和大气压光电离质谱仪对辛醇和缓冲相进行定量。该方法每批 96 个化合物的通量为两天。该方法已使用 72 种具有不同离子化和 LogD 值（-2 至+6）的文献化合物进行了验证。观察到的决定系数 r(2)为 0.9973。
