School of Pharmacy, College of Medicine, National Taiwan University, Taiwan.
J Chromatogr A. 2012 Feb 24;1226:48-54. doi: 10.1016/j.chroma.2011.08.012. Epub 2011 Aug 12.
The high morbidity and mortality associated with invasive fungal infections have increased the importance of improving treatment efficacy. Posaconazole is a novel agent with strong antifungal activity and low toxicity. The success of posaconazole pharmacotherapy strongly depends on precise controlling of concentration of the drug in the blood. In the present study, a solid phase extraction-capillary electrophoresis (SPE-CE) method was developed for rapid and accurate determination of posaconazole in the plasma of patients. We used the field-amplified sample stacking (FASS) technique to improve the sensitivity of CE, and applied the SPE procedures to reduce the matrix effect that was frequently encountered by biological samples in FASS system. Effect of filter types on the recovery rate of compounds with high lipophilicity was carefully investigated. Parameters affecting FASS performance were all optimized to obtain the best sensitivity with the highest speed. When using 1.25 M formic acid as the background electrolyte and 0.2 M formic acid in 95% (v/v) methanol as the sample solution, the limit of detection (LOD) for posaconazole was 10 ngmL(-1), with an analytical run time of less than 5 min. The relative standard deviation (RSD) of the peak area ratios for repeatability (intra-day, n=6) and intermediate precision (inter-day, n=3) were lower than 7.2% and 7.5%, respectively. The accuracy was tested by recovery, and the recovery rates were within 95.1% and 106.4%, respectively. The successful application of the developed method demonstrated its feasibility as an effective method for clinical use.
侵袭性真菌感染相关的高发病率和死亡率增加了提高治疗效果的重要性。泊沙康唑是一种具有强大抗真菌活性和低毒性的新型药物。泊沙康唑药物治疗的成功在很大程度上取决于精确控制血液中药物的浓度。在本研究中，开发了一种固相萃取-毛细管电泳（SPE-CE）方法，用于快速准确地测定患者血浆中的泊沙康唑。我们使用场放大样品堆积（FASS）技术来提高 CE 的灵敏度，并应用 SPE 程序来减少生物样品在 FASS 系统中经常遇到的基质效应。仔细研究了不同滤器类型对高亲脂性化合物回收率的影响。优化了影响 FASS 性能的参数，以获得最高速度下的最佳灵敏度。当使用 1.25 M 甲酸作为背景电解质，95%（v/v）甲醇中的 0.2 M 甲酸作为样品溶液时，泊沙康唑的检测限（LOD）为 10 ngmL(-1)，分析运行时间少于 5 分钟。峰面积比的重复性（日内，n=6）和中间精密度（日间，n=3）的相对标准偏差（RSD）均低于 7.2%和 7.5%。通过回收率测试了准确性，回收率在 95.1%和 106.4%之间。该方法的成功应用证明了其作为一种有效的临床应用方法的可行性。
