索磷布韦强制降解产物的稳定性指示方法及液相色谱-串联质谱表征
Stability-Indicating Method and LC-MS-MS Characterization of Forced Degradation Products of Sofosbuvir.
作者信息
Nebsen M, Elzanfaly Eman S
机构信息
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr-El Aini Street, 11562 Cairo, Egypt.
Center of Applied Research and Advanced Studies, Faculty of Pharmacy, Cairo University, Kasr-El Aini Street, 11562 Cairo, Egypt.
出版信息
J Chromatogr Sci. 2016 Oct 17;54(9):1631-1640. doi: 10.1093/chromsci/bmw119.
Sofosbuvir is a novel direct acting antiviral agent against hepatitis C virus. In the present work, a rapid, specific and reproducible isocratic reversed phase high performance liquid chromatography (RP-HPLC) method has been developed and validated for the determination of sofosbuvir in the presence of its stressed degradation products. Sobosbuvir was subjected to hydrolysis (acidic, alkaline and neutral), oxidation, photolysis and thermal stress, as per international conference on harmonization (ICH) conditions. The drug showed degradation under oxidative, photolysis, acid and base hydrolysis stress conditions. However, it was stable under thermal and neutral hydrolysis stress conditions. Chromatographic separation of the drug from its degradation products was performed on Inertsil ODS-3 C18 (250 mm × 4.6 mm i.d., 5 µm) column using a green mobile phase of methanol:water 70:30 (v/v). The degradation products were characterized by LC-MS-MS and the fragmentation pathways were proposed. The developed method was validated as per ICH guidelines. No previous method was reported regarding the degradation behavior of sofosbuvir.
索磷布韦是一种新型的抗丙型肝炎病毒直接作用抗病毒药物。在本研究中，已开发并验证了一种快速、特异且可重现的等度反相高效液相色谱（RP-HPLC）方法，用于在其强制降解产物存在的情况下测定索磷布韦。按照国际协调会议（ICH）的条件，对索磷布韦进行了水解（酸性、碱性和中性）、氧化、光解和热应激试验。该药物在氧化、光解、酸和碱水解应激条件下会发生降解。然而，它在热应激和中性水解应激条件下是稳定的。使用甲醇:水70:30（v/v）的绿色流动相，在Inertsil ODS-3 C18（250 mm×4.6 mm内径，5 µm）柱上对该药物与其降解产物进行了色谱分离。通过LC-MS-MS对降解产物进行了表征，并提出了裂解途径。所开发的方法按照ICH指南进行了验证。此前未见有关索磷布韦降解行为的方法报道。
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