创药における溶解性スクリーニング法の开发 development of - j-stage.pdf

YAKUGAKU ZASSHI 122(3) 237―246 (2002)  2002 The Pharmaceutical Society of Japan 237237 ―Regular Articles― 創薬における溶解性スクリーニング法の開発 菅谷幸子，吉葉孝子，梶間 隆，石濱 泰 Development of Solubility Screening Methods in Drug Discovery Yukiko SUGAYA , Takako YOSHIBA , Takashi KAJIMA , and Yasushi ISHIHAMA Department of Physical Chemistry, Analytical Research Laboratories, Eisai Co., Ltd., 5  1 3, Tokodai, Tsukuba, Ibaraki 300 2635, Japan ( ) Received September 6, 2001; Accepted December 25, 2001 We developed two methods for solubility screening of drug candidates in drug discovery. The ˆrst is a solution ( ) precipitation SP method, in which the sample solutions are prepared by adding the drug solution in dimethylsulfoxide ( )  DMSO to buŠers followed by ˆltering oŠ the precipitate using 96-well ˆlterplate. The second is a powder dissolution ( ) PD method, in which the solid samples are dissolved to the buŠer in the HPLC vial equipped with the ˆlter membrane in the HPLC autosampler. An HPLC equipped with a photodiode array detector is used to measure the concentration of the sample solutions in both methods. The SP method was used for high throughput screening the solvating process of the candidates in aqueous solutions with lower sample consumption, and the PD method was used for screening both in- ter molecular interaction in solid state and solvation in aqueous solution with more sample amount than that of SP metho