Tipranavir (TPV) is one of the most recently developed protease inhibitors (PI) and it is specially recommended for treatment-experienced patients who are resistant to other PI drugs. In this work, a simple and friendly environmental CZE stability-indicating method to assay TPV capsules was developed and two TPV organic impurities were identified by high resolution mass spectrometry (HRMS). The optimized analytical conditions were: background electrolyte composed of sodium borate 50 mM, pH 9.0 and 5% of methanol; voltage + 28 kV; hydrodynamic injection of 5 s (100 mbar), detection wavelength 240 nm, at 25 °C. The separation was achieved in a fused silica capillary with 50 µm × 40 cm (inner diameter × effective length), using furosemide as internal standard. All the validation parameters were met and the method was specific, even in the presence of degradation products and impurities. Oxidation was indicated as the main degradation pathway among those evaluated in this study (acidic, alkaline, thermal, photolytic and oxidative) and it showed a second order degradation kinetic, under the conditions used in this study. The main oxidation product and an organic impurity detected in the standard were characterized by Q-TOF, and both of them correspond to oxidation products of TPV.

Tipranavir（TPV）是最近开发的蛋白酶抑制剂（PI）之一，特别推荐用于对其他PI药物有抗药性的有治疗经验的患者。在这项工作中，开发了一种简单而友好的环境CZE稳定性指示方法来测定TPV胶囊，并通过高分辨率质谱（HRMS）鉴定了两种TPV有机杂质。优化的分析条件为：背景电解质，由50 mM硼酸钠，pH 9.0和5％的甲醇组成；电压+ 28 kV; 在25°C下进行5 s（100 mbar）的流体动力注入，检测波长为240 nm。使用呋塞米作为内标，在50 µm×40 cm（内径×有效长度）的熔融石英毛细管中完成分离。满足所有验证参数，并且方法是特定的，即使存在降解产物和杂质。在这项研究中所评估的那些（酸性，碱性，热，光解和氧化）中，氧化被认为是主要的降解途径，并且在该研究所用的条件下，它表现出二级降解动力学。用Q-TOF对标准品中检测到的主要氧化产物和有机杂质进行了表征，它们均对应于TPV的氧化产物。