Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, Belgrade, Serbia.
Spectrochim Acta A Mol Biomol Spectrosc. 2010 Feb;75(2):930-5. doi: 10.1016/j.saa.2009.12.043. Epub 2009 Dec 16.
A novel topical corticosteroid FA-21-PhP, 2-phenoxypropionate ester of fluocinolone acetonide, has been synthesized in order to investigate the possibility of decreasing systemic side effects. In this study model system for in vitro solvolytic reaction of FA-21-PhP has been analyzed in ethanol/water (90:10, v/v) with excess of sodium hydrogen carbonate. The selected conditions have been used as in vitro model for activation of corticosteroid C-21 ester prodrug. The second-order derivative spectrophotometric method (DS) using zero-crossing technique was developed for monitoring ternary mixture of solvolysis. Fluocinolone acetonide (FA) as a solvolyte was determined in the mixture in the concentration range 0.062-0.312 mM using amplitude (2)D(274.96). Experimentally determined LOD value was 0.0295 mM. The accuracy of proposed DS method was confirmed with HPLC referent method. Peak area of parent ester FA-21-PhP was used for solvolysis monitoring to ensure the initial stage of changes. Linear relationship in HPLC assay for parent ester was obtained in the concentration range 0.054-0.54 mM, with experimentally determined LOD value of 0.0041 mM. Investigated solvolytic reaction in the presence of excess of NaHCO(3) proceeded via a pseudo-first-order kinetic with significant correlation coefficients 0.9891 and 0.9997 for DS and HPLC, respectively. The values of solvolysis rate constant calculated according to DS and HPLC methods are in good accordance 0.038 and 0.043 h(-1), respectively.
为了研究降低全身副作用的可能性，合成了一种新型局部皮质类固醇 FA-21-PhP，即氟轻松丙酮缩 2-苯氧基丙酸酯。
在本研究中，分析了 FA-21-PhP 在乙醇/水（90:10，v/v）中与过量碳酸氢钠的体外溶剂分解反应模型系统。选择的条件已被用作皮质甾类 C-21 酯前药的体外激活模型。
二阶导数分光光度法（DS）结合零交叉技术被开发用于监测溶剂分解的三元混合物。使用幅度（2）D（274.96）在 0.062-0.312 mM 浓度范围内测定溶剂分解混合物中的氟轻松丙酮缩 21 酯（FA）。实验确定的检测限为 0.0295 mM。用 HPLC 参考方法验证了所提出的 DS 方法的准确性。用峰面积监测原酯 FA-21-PhP 的分解，以确保变化的初始阶段。在 HPLC 测定中，原酯的线性关系在 0.054-0.54 mM 浓度范围内得到，实验确定的检测限为 0.0041 mM。
在过量 NaHCO3 的存在下进行的溶剂分解反应通过拟一级动力学进行，DS 和 HPLC 的相关系数分别为 0.9891 和 0.9997，具有显著相关性。根据 DS 和 HPLC 方法计算的溶剂分解速率常数分别为 0.038 和 0.043 h-1，这两个值非常吻合。
