Sobczak Agnieszka, Teżyk Artur, Szyndlarewicz Joanna, Ziarniak Jan, Świątek Piotr, Malinka Wiesław
Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, 6 Grunwaldzka Str., 60-780 Poznań, Poland.
Department of Forensic Medicine, Poznan University of Medical Sciences, 6 Święcickiego Str., 60-780 Poznań, Poland.
Med Chem Res. 2017;26(10):2443-2451. doi: 10.1007/s00044-017-1944-4. Epub 2017 Jun 15.
Hydrochloride of 10-{2-hydroxy-3-[,-bis-(2-hydroxyethyl)amino]propyl}-2-trifluoromethylphenothiazine (Flu-A) is a analogue of neuroleptic fluphenazine. Flu-A exhibits anti-multidrug resistance, antimutagenic, proapoptopic, and cancer-chemopreventive activities in screening studies. To define identity, quality, and purity of new active substance it is necessary to develop a appropriate analytical method and to establish a degradation profile. Thus, a stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for quantitative determination of Flu-A in the presence of its degradation products generated under stress conditions. The compound was subjected to oxidation, photolysis, and degradation in aqueous solutions (neutral and acidic), and solid state according to the International Council for Harmonisation Guidelines. The method was also found to be suitable for intermediate and accelerated studies and for the evaluation of kinetic mechanism of Flu-A degradation in aqueous solutions (pH 5.1-7.5, 353 K). The structures of main potential degradation products were established using high-performance liquid chromatography-Electrospray Ionization-mass spectrometry method.
10-{2-羟基-3-[,-双-(2-羟乙基)氨基]丙基}-2-三氟甲基吩噻嗪盐酸盐（Flu-A）是抗精神病药物氟奋乃静的类似物。在筛选研究中，Flu-A表现出抗多药耐药性、抗诱变、促凋亡和癌症化学预防活性。为了确定新活性物质的特性、质量和纯度，有必要开发一种合适的分析方法并建立降解图谱。因此，开发并验证了一种稳定性指示反相高效液相色谱法，用于在应激条件下生成的降解产物存在的情况下定量测定Flu-A。根据国际协调理事会指南，该化合物在水溶液（中性和酸性）和固态中进行氧化、光解和降解。该方法还适用于中间研究和加速研究，以及评估Flu-A在水溶液（pH 5.1-7.5，353 K）中的降解动力学机制。使用高效液相色谱-电喷雾电离-质谱法确定了主要潜在降解产物的结构。
