Iran Polymer and Petrochemical Institute , Tehran , Islamic Republic of Iran.
Drug Dev Ind Pharm. 2014 Apr;40(4):519-26. doi: 10.3109/03639045.2013.771646. Epub 2013 Apr 17.
In the present study, the aqueous stability of taxol in different aqueous media and immiscible aqueous/organic systems at 37 °C was investigated. The aqueous media included phosphate buffered saline (PBS) and PBS containing 10% methanol, 10% ethanol, 10% hydroxypropyl β-cyclodextrin (HP-βCD), 1% sodium citrate and 1% Tween 80. The immiscible systems consisted of PBS/octanol, PBS/dichloromethane, PBS/chloroform and PBS/ethyl acetate. The concentrations of taxol and related derivatives in each of the media were determined through the high-performance liquid chromatography assay. Results showed that hydrolysis and epimerization were two major types of degradation for taxol in the aqueous media starting from the initial hours of contact (6 hours). Addition of Tween 80 to PBS moderately increased the aqueous stability of taxol. As well, using PBS containing 10% HP-βCD inhibited the taxol hydrolysis, while epimerization still in process. In the case of immiscible systems, except for PBS/ethyl acetate system, no evidences of taxol hydrolysis were observed. Meanwhile, epimerization of taxol in PBS/dichloromethane and PBS/chloroform systems underwent due to the ability of C-Cl bonds to form hydrogen bonding with the hydroxyl group of C7 of taxol.
在本研究中,考察了紫杉醇在不同水介质和不混溶水/有机体系中在 37°C 时的水稳定性。水介质包括磷酸盐缓冲盐水 (PBS) 和含 10%甲醇、10%乙醇、10%羟丙基-β-环糊精 (HP-βCD)、1%柠檬酸钠和 1%吐温 80 的 PBS。不混溶体系由 PBS/正辛醇、PBS/二氯甲烷、PBS/氯仿和 PBS/乙酸乙酯组成。通过高效液相色谱法测定每种介质中紫杉醇和相关衍生物的浓度。结果表明,从接触的最初几个小时(6 小时)开始,水解和差向异构化是紫杉醇在水介质中的两种主要降解类型。向 PBS 中添加吐温 80 可适度提高紫杉醇的水稳定性。同样,使用含 10% HP-βCD 的 PBS 抑制了紫杉醇的水解,而差向异构化仍在进行中。对于不混溶体系,除了 PBS/乙酸乙酯体系外,未观察到紫杉醇水解的证据。同时,由于 C-Cl 键能够与紫杉醇 C7 位的羟基形成氢键,因此在 PBS/二氯甲烷和 PBS/氯仿体系中紫杉醇发生了差向异构化。