Chadha Renu, Bali Alka, Bansal Gulshan
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Punjab University, Chandigarh 160014, India.
University Institute of Pharmaceutical Sciences, UGC Center of Advanced Study, Punjab University, Chandigarh 160014, India.
J Pharm Biomed Anal. 2016 Jan 25;118:139-148. doi: 10.1016/j.jpba.2015.10.028. Epub 2015 Oct 26.
Dronedarone HCl was subjected to forced decomposition conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as suggested in the ICH guideline Q1A(R2). The drug showed significant degradation under alkaline hydrolytic and alkaline photolytic conditions while it remained stable in neutral, acidic, thermal and oxidative conditions. In total, six degradation products (I-VI) were formed, which could be separated by chromatography on C18 (250 mm × 4.6 mm; 5 μ, Xterra) column using isocratic elution method. Detection wavelength was selected as 288 nm. Multi-stage (MS(n)) and MS/TOF accurate mass studies were carried out to establish the complete fragmentation pathway of the drug which in turn was utilized in characterization of the products. The degradation pathway of the drug leading to generation of products I-VI was postulated and this has not been reported so far.
按照国际人用药品注册技术协调会（ICH）指南Q1A(R2)的建议，对盐酸决奈达隆进行了水解（中性、酸性和碱性）、氧化、光解和热应激等强制降解试验。该药物在碱性水解和碱性光解条件下显示出显著降解，而在中性、酸性、热和氧化条件下保持稳定。总共形成了六种降解产物（I - VI），可采用等度洗脱法在C18（250 mm×4.6 mm；5 μ，Xterra）柱上进行色谱分离。检测波长选择为288 nm。进行了多级（MS(n)）和MS/TOF精确质量研究，以确定药物的完整裂解途径，进而用于产物的表征。推测了导致生成产物I - VI的药物降解途径，且该途径迄今尚未见报道。
