Evaluation of degradation kinetics and physicochemical stability of tenofovir.
Evaluation of degradation kinetics and physicochemical stability of tenofovir.
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DOI：
10.1002/dta.1656
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发表时间：
2015-03
影响因子：
2.9
通讯作者：
Youan, Bi-Botti C.
中科院分区：
文献类型：
--
作者：
Agrahari, Vivek;Putty, Sandeep;Mathes, Christiane;Murowchick, James B.;Youan, Bi-Botti C.
替诺福韦(TFV)已被证明可以防止人类免疫缺陷病毒(HIV)通过阴道传播。但是，关于它在各种储存和应力条件下的稳定性的信息很少。因此，本研究旨在利用液相色谱质谱(LC-MS)和固体X射线衍射法(XRD)研究TFV的降解行为和理化稳定性。LC-MS分析在QTrap质谱仪上进行，增强质谱图(EMS)扫描为正模式。采用反相C18柱作为固定相。TFV在酸性和碱性条件下均表现出降解作用。M/z为289.2和170amu的降解产物分别为TFV的6-羟基腺嘌呤衍生物和(2-羟丙基-2-氧基)甲基膦酸。用拟一级降解动力学方程估算了90%的降解值在酸性条件下为3.84、25.34和84.22h，在碱性条件下为58.26、384.49和1277.75 h所需的保质期、半衰期和时间。在pH值为4.5(正常宫颈阴道pH)和3%和30%v/v双氧水的氧化应激条件下，未观察到明显降解。用Arrhenius图计算出TFV粉剂在室温下的保质期为23个月。X射线衍射图表明，药物在加速和热应力条件下稳定，并保持其原有的结晶度。稳定性分析表明，TFV在各种胁迫条件下都是稳定的，但在强酸性和碱性环境中应采取配方策略来保护它。
Tenofovir (TFV) has been proven to prevent the transmission of the Human Immunodeficiency Virus (HIV) through the vagina. But, there is little information available about its stability under various storage and stress conditions. Hence, this study aimed to investigate the degradation behavior and physicochemical stability of TFV using liquid chromatography coupled mass spectrometry (LC-MS) and solid state X-ray diffraction (XRD) analyses. The LC-MS analysis was performed on a QTrap mass spectrometer with an enhanced mass spectrum (EMS) scan in positive mode. A reversed phase C18 column was used as the stationary phase. TFV exhibited degradation under acidic and alkaline hydrolytic conditions. The degradation products with m/z 289.2 and 170 amu have been proposed as 6-Hydroxy adenine derivative of TFV, and (2-hydroxypropan-2-yloxy) methylphosphonic acid, respectively. A pseudo-first-order degradation kinetic allowed for estimating the shelf-life, half-life, and time required for 90% degradation values of 3.84,25.34, and 84.22 h in acidic conditions, and 58.26,384.49, and 1277.75 h in alkaline conditions, respectively. No significant degradation was observed at pH 4.5 (normal cervicovaginal pH) and oxidative stress conditions of 3% and 30% v/v hydrogen peroxide solution. The shelf life of TFV powder at room temperature was 23 months as calculated by using an Arrhenius plot. The XRD pattern showed that the drug was stable and maintained its original crystallinity under the accelerated and thermal stress conditions applied. Stability analyses revealed that the TFV was stable in various stress conditions; however, formulation strategies should be implemented to protect it in strong acidic and alkaline environments.
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DOI：
10.1016/s1570-0232(03)00333-7
发表时间：
2003-08-15
影响因子：
3
作者：
Sentenac, S;Fernandez, C;Aymard, G
通讯作者：
Aymard, G
DOI：
10.1016/j.jpba.2012.10.023
发表时间：
2013-02-23
影响因子：
3.4
作者：
Shah, Syeda A. B.;Mullin, Rebecca;Naughton, Declan P.
通讯作者：
Naughton, Declan P.
影响因子：
1.3
作者：
Choi, S. O.;Rezk, N.;Kashuba, A. D. M.
通讯作者：
Kashuba, A. D. M.
影响因子：
3.3
作者：
Cooper, VB;Pearce, GES;Petts, CR
通讯作者：
Petts, CR
用于测定猴血浆中替诺福韦的 LC/MS/MS 方法的开发和验证
影响因子：
2
作者：
Guo, Jifen;Meng, Fanhua;Zhao, Yimin
通讯作者：
Zhao, Yimin