Analytical Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut, Egypt.
Spectrochim Acta A Mol Biomol Spectrosc. 2018 Sep 5;202:50-57. doi: 10.1016/j.saa.2018.05.044. Epub 2018 May 16.
A rapid and specific spectrofluorimetric method with higher sensitivity was developed for determination of ledipasvir (LDS) in tablets and human plasma. The proposed method relies on hydrogen bonding formations between the hydroxyl groups of polyoxyethylene 50 stearate and LDS, causing significant enhancement of its native fluorescence. The fluorescence intensity was measured at 430 nm after excitation at 340 nm. The fluorescence-concentration plot was rectilinear over the range 1-400 ng mL with detection and quantification limits of 0.25 and 1.10 ng mL, respectively. The high sensitivity of the proposed method permits its application for ledipasvir determinations in real human plasma even in the presence of co-administered drugs sofosbuvir and ribavirin. Moreover, the proposed method was further extended to stability studies of ledipasvir after exposure to different forced degradation conditions according to ICH guidelines, along with the structural elucidation of its degradation products utilizing IR and Mass spectra. A proposal for the degradation pathways was presented.
开发了一种快速、灵敏且具有特异性的荧光分光光度法，用于测定片剂和人血浆中的来迪派韦（LDS）。该方法依赖于硬脂酸聚氧乙烯 50 酯中羟基与 LDS 之间的氢键形成，导致其本征荧光显著增强。在 340nm 激发下，于 430nm 处测量荧光强度。荧光-浓度曲线在 1-400ng/mL 范围内呈线性，检测限和定量限分别为 0.25 和 1.10ng/mL。该方法灵敏度高，即使在同时给予药物索非布韦和利巴韦林的情况下，也可用于测定真实人血浆中的来迪派韦。此外，根据 ICH 指南，该方法进一步扩展到来迪派韦在不同强制降解条件下的稳定性研究，同时利用 IR 和质谱对其降解产物进行结构阐明。提出了降解途径的建议。
