Sadutto Daniele, Mammone Francesca Romana, D'Ettorre Giulia, Zanitti Leo, De Orsi Daniela, Alfonsi Romina, Prestinaci Francesca, Cirilli Roberto
Centre for the Control and Evaluation of Medicines, Chemical Medicines Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Molecules. 2025 Apr 29;30(9):1966. doi: 10.3390/molecules30091966.
A direct enantio- and chemo-selective high-performance liquid chromatographic method was developed for determining the enantiomeric impurity of the chiral active pharmaceutical ingredient silodosin. The simultaneous separation of enantiomers of silodosin and its main organic related substances listed in the Japanese Pharmacopoeia (JP) monograph for drug substance was achieved on Chiralpak AD-3 (250 mm × 4.6 mm, 3 μm) column under normal-phase isocratic conditions. The optimized conditions employed the mixture -heptane-ethanol-diethylamine (70:30:0.1) (//) as a mobile phase and a temperature of 35 °C. The complete separation of the enantiomers of silodosin and its main impurities was obtained within 12 min. The chromatographic method has been validated according to the International Conference on Harmonization (ICH) guidelines and compared with the method reported in the JP monograph. The standard curve for silodosin exhibited linearity (R > 0.999) within the concentration range of 1.13-2500 µg mL. The Chiralpak AD-3 has demonstrated a remarkable level of efficiency, enabling the attainment of limits of quantitation for silodosin of 1.13 µg mL (equivalent to 0.057% of a sample solution of 2 mg mL) and ranging from 0.48 µg mL to 1.94 µg mL for other impurities.
建立了一种直接对映体和化学选择性高效液相色谱法，用于测定手性活性药物成分西洛多辛的对映体杂质。在正相等度条件下，于Chiralpak AD-3（250 mm×4.6 mm，3μm）色谱柱上实现了西洛多辛对映体及其在日本药典（JP）原料药专论中列出的主要有机相关物质的同时分离。优化条件采用正庚烷-乙醇-二乙胺（70:30:0.1）（v/v/v）混合溶液作为流动相，温度为35℃。在12分钟内实现了西洛多辛对映体及其主要杂质的完全分离。该色谱方法已根据国际协调会议（ICH）指南进行了验证，并与JP专论中报道的方法进行了比较。西洛多辛的标准曲线在1.13 - 2500μg/mL的浓度范围内呈线性（R＞0.999）。Chiralpak AD-3表现出了显著的分离效率，西洛多辛的定量限达到1.13μg/mL（相当于2mg/mL样品溶液的0.057%），其他杂质的定量限在0.48μg/mL至1.94μg/mL之间。
