Saibaba B, Vishnuvardhan Ch, Johnsi Rani P, Satheesh Kumar N
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research, Balanagar, Hyderabad 500 037, Telangana, India.
J Chromatogr Sci. 2018 Jan 1;56(1):6-17. doi: 10.1093/chromsci/bmx074.
Almotriptan maleate (ALMT), a highly selective 5-hydroxy tryptamine 1B/1D (5-HT1B/1D) receptor agonist used in the treatment of migraine headache was subjected to various ICH (Q1A (R2)) specified guidelines. The drug underwent significant degradation under hydrolytic (acid, base and neutral), oxidative and photolytic stress conditions, while it was stable under thermal stress condition. A total of seven significant degradation products (DPs) were obtained. A simple, selective and reliable UPLC method has been developed for the separation of ALMT and its DPs using Acquity UPLC HSS Cyano (100 × 2.1 mm, 1.8 μm) column with mobile phase consisting of ammonium acetate (10 mM, pH 4.4) buffer and acetonitrile in gradient elution mode. Chromatographic analysis was performed at a flow rate of 0.3 mL/min using a PDA detector at a wavelength of 230 nm. All the DPs (DP-1 to DP-7) were characterized using UHPLC-ESI-QTOF based on mass fragmentation pattern and accurate m/z values. The developed UPLC method was validated in terms of specificity, linearity, precision and accuracy. The developed stability-indicating method helps in quantification of drug in the presence of DPs.
马来酸阿莫曲坦（ALMT）是一种用于治疗偏头痛的高选择性5-羟色胺1B/1D（5-HT1B/1D）受体激动剂，已按照国际协调会议（ICH）（Q1A（R2））规定的各项指南进行了研究。该药物在水解（酸、碱和中性）、氧化和光解应激条件下会发生显著降解，而在热应激条件下则稳定。总共获得了七种显著降解产物（DPs）。已开发出一种简单、选择性且可靠的超高效液相色谱（UPLC）方法，用于分离ALMT及其DPs，采用Acquity UPLC HSS Cyano（100×2.1 mm，1.8μm）色谱柱，流动相由醋酸铵（10 mM，pH 4.4）缓冲液和乙腈组成，采用梯度洗脱模式。使用二极管阵列检测器（PDA）在波长230 nm处，以0.3 mL/min的流速进行色谱分析。基于质量碎片模式和精确的m/z值，使用超高效液相色谱-电喷雾电离-四极杆飞行时间质谱（UHPLC-ESI-QTOF）对所有DPs（DP-1至DP-7）进行了表征。所开发的UPLC方法在特异性、线性、精密度和准确度方面进行了验证。所开发的稳定性指示方法有助于在存在DPs的情况下对药物进行定量分析。
