Song D, Hsu L F, Au J L
College of Pharmacy, Ohio State University, Columbus 43210, USA.
J Pharm Sci. 1996 Jan;85(1):29-31. doi: 10.1021/js950286j.
This study examined the stability and protein binding of taxol in aqueous solution and tissue culture medium. After storage for 19 h in 1% methanolic aqueous solution, the concentration of taxol declined to about 40% in 1.5 mL glass vials, 67% in 1.5 mL polypropylene tubes, and 55% in 1.5 mL siliconized polypropylene tubes. There was no difference in the decline at two initial concentrations of 0.18 and 1.8 micrograms/mL. The concentration declines were biphasic; the initial phase showed a half-life of 1-2 min and the second phase showed a half-life of 30-350 min. A methanol wash recovered 0%, 16%, and 31% of taxol from glass vials and unsiliconized and siliconized polypropylene tubes, respectively. In culture medium without fetal bovine serum, the concentration of taxol stored in polystyrene tissue culture plates declined to 73% after 24 h, whereas no concentration decline was observed in the presence of 9% fetal bovine serum (FBS). Protein binding of taxol in FBS-containing culture medium was saturable, varying from 79% at 0.5 microgram/mL to 20% at 15 micrograms/mL. These data indicated (a) rapid and nonspecific adsorption of taxol to plastic and glass surfaces, (b) stabilization of taxol in culture medium by FBS, and (c) saturable protein binding of taxol in culture medium.
本研究检测了紫杉醇在水溶液和组织培养基中的稳定性及蛋白结合情况。在1%甲醇水溶液中储存19小时后,1.5毫升玻璃小瓶中紫杉醇浓度降至约40%,1.5毫升聚丙烯管中降至67%,1.5毫升硅化聚丙烯管中降至55%。在0.18和1.8微克/毫升这两个初始浓度下,浓度下降情况无差异。浓度下降呈双相;初始阶段半衰期为1 - 2分钟,第二阶段半衰期为30 - 350分钟。甲醇洗涤分别从玻璃小瓶、未硅化和硅化的聚丙烯管中回收了0%、16%和31%的紫杉醇。在不含胎牛血清的培养基中,储存在聚苯乙烯组织培养板中的紫杉醇浓度在24小时后降至73%,而在存在9%胎牛血清(FBS)的情况下未观察到浓度下降。含FBS的培养基中紫杉醇的蛋白结合具有饱和性,从0.5微克/毫升时的79%变化到15微克/毫升时的20%。这些数据表明:(a)紫杉醇对塑料和玻璃表面有快速且非特异性的吸附;(b)FBS可使培养基中的紫杉醇稳定;(c)培养基中紫杉醇的蛋白结合具有饱和性。