Stability behaviour of antiretroviral drugs and their combinations. 4: Characterization of degradation products of tenofovir alafenamide fumarate and comparison of its degradation and stability behaviour with tenofovir disoproxil fumarate
Stability behaviour of antiretroviral drugs and their combinations. 4: Characterization of degradation products of tenofovir alafenamide fumarate and comparison of its degradation and stability behaviour with tenofovir disoproxil fumarate
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DOI：
10.1016/j.jpba.2016.08.022
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发表时间：
2016-11-30
影响因子：
3.4
通讯作者：
Singh, Saranjit
中科院分区：
文献类型：
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作者：
Golla, Vijaya Madhyanapu;Kurmi, Moolchand;Singh, Saranjit
在这项研究中，研究了替诺福韦的新型前药富马酸替诺福韦艾拉酚胺（TAF）的应激降解行为，并与目前使用的前药同类物富马酸替诺福韦二异丙酯（TDF）进行了比较，TDF的内在稳定性由我们早期报道[14]。此外，还对两种药物进行了pH稳定性和胃肠道稳定性研究。TAF强制降解样品的高效液相色谱（HPLC）分析显示形成了6种降解产物（DP），而TDF（RSCAv.5（2015）96117-96129）的早期特征为12种。与TDF一样，通过使用复杂的联用液相色谱-高分辨率质谱（LC-HRMS）和多级质谱（MSn）工具对TAF的DP进行表征。pH 1.2-10之间的pH稳定性研究显示TAF具有更高的稳定性，除了在酸性条件下TAF被广泛降解。在模拟胃液（SGF）、模拟肠液（SIF）和进食状态模拟胃液（FeSSGF）中的胃肠道稳定性研究表明，TAF必须在进食状态下给药，因为与酸性pH和SGF中的大量损失相比，药物在FeSSGF中实际上是稳定的。(C)2016爱思唯尔B. V.保留所有权利。
In this study, stress-degradation-behaviour of tenofovir alafenamide fumarate (TAF), a novel prodrug of tenofovir, was investigated and compared with currently used prodrug congener, tenofovir disoproxil fumarate (TDF), whose intrinsic stability was reported by us earlier [14]. Also, pH stability and gastrointestinal stability studies were conducted on both the drugs. High performance liquid chromatography (HPLC) analysis of stressed samples of TAF revealed formation of six degradation products (DPs) against twelve characterized earlier in the case of TDF (RSCAdv.5(2015)96117-96129). Like TDF, characterization of DPs of TAF was done by using sophisticated hyphenated liquid chromatography-high resolution mass spectrometry (LC-HRMS) and multistage mass spectrometry (MSn) tools. pH-stability studies between pH 1.2-10 revealed greater stability of TAF, except in acidic conditions, where TAF was degraded extensively. Investigation of gastrointestinal stability in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and fed state simulated gastric fluid (FeSSGF) suggested that TAF must be administered in fed state, as the drug was practically stable in FeSSGF as compared to extensive loss at acidic pH and in SGF. (C) 2016 Elsevier B.V. All rights reserved.