Jabbaribar Farnaz, Mortazavi Alireza, Jalali-Milani Reza, Jouyban Abolghasem
Drug Applied Research Centre, Tabriz University (Medical Sciences), Tabriz, Iran.
Chem Pharm Bull (Tokyo). 2008 Dec;56(12):1639-44. doi: 10.1248/cpb.56.1639.
A simple and rapid micellar electrokinetic chromatography (MEKC) method was developed for the analysis of an antiviral drug, oseltamivir, and its hydrolyzed product in Tamiflu capsules. Background electrolytes consisted of boric acid 10 mM, pH 10, and sodium dodecyl sulphate (SDS) 40 mM. The limit of detection (LOD) and limit of quantification (LOQ) of oseltamivir were 1.7 and 8.0 microg/ml, respectively. MEKC sweeping in a high electroosmotic flow environment for neutral analytes was also utilized to improve the sensitivity of the assay. In MEKC-sweeping mode, a buffer comprising boric acid 30 mM, pH 10, and SDS 50 mM was used. A 17-fold increase in detection sensitivity was achieved with the MEKC-sweeping method compared with the MEKC mode. Unlike in MEKC, the LOD and LOQ for oseltamivir were 0.1 and 0.3 microg/ml, respectively, using the MEKC-sweeping method. Both methods were successful in determining oseltamivir concentration in its capsule formulation, and the MEKC-sweeping method was capable of determination of the drug at lower concentrations. The hydrolyzed product of oseltamivir (oseltamivir carboxylate) was also detected using the MEKC method. Our observations revealed that the prodrug could be hydrolyzed to the active compound at alkaline pH within ca. 60 min.
建立了一种简单快速的胶束电动毛细管色谱法(MEKC),用于分析抗病毒药物奥司他韦及其在泰诺福韦胶囊中的水解产物。背景电解质由10 mM硼酸(pH 10)和40 mM十二烷基硫酸钠(SDS)组成。奥司他韦的检测限(LOD)和定量限(LOQ)分别为1.7和8.0 μg/ml。还利用在高电渗流环境中对中性分析物进行MEKC扫集来提高测定的灵敏度。在MEKC扫集模式下,使用了一种由30 mM硼酸(pH 10)和50 mM SDS组成的缓冲液。与MEKC模式相比,MEKC扫集法的检测灵敏度提高了17倍。与MEKC不同,使用MEKC扫集法时,奥司他韦的LOD和LOQ分别为0.1和0.3 μg/ml。两种方法都成功地测定了其胶囊制剂中奥司他韦的浓度,并且MEKC扫集法能够测定更低浓度的药物。还使用MEKC法检测了奥司他韦的水解产物(奥司他韦羧酸盐)。我们的观察结果表明,前药在碱性pH条件下约60分钟内可水解为活性化合物。