Campestre Cristina, Locatelli Marcello, Guglielmi Paolo, De Luca Elisa, Bellagamba Giuseppe, Menta Sergio, Zengin Gokhan, Celia Christian, Di Marzio Luisa, Carradori Simone
a Department of Pharmacy , University of Chieti - Pescara "G. d'Annunzio" , Chieti , Italy.
b Interuniversity Consortium of Structural and Systems Biology , Rome , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):1-11. doi: 10.1080/14756366.2017.1354858.
This paper reports the MEPS-HPLC-DAD method for the simultaneous determination of 12 azole drugs (bifonazole, butoconazole, clotrimazole, econazole, itraconazole, ketoconazole, miconazole, posaconazole, ravuconazole, terconazole, tioconazole and voriconazole) administered to treat different systemic and topical fungal infections, in biological samples. Azole drugs separation was performed in 36 min. The analytical method was validated in the ranges as follows: 0.02-5 μg mL for ravuconazole; 0.2-5 μg mL for terconazole; 0.05-5 μg mL for the other compounds. Human plasma and urine were used as biological samples during the analysis, while benzyl-4-hydroxybenzoate was used as an internal standard. The precision (RSD%) and trueness (Bias%) values fulfill with International Guidelines requirements. To the best of our knowledge, this is the first HPLC-DAD procedure coupled to MEPS, which provides the simultaneous analysis of 12 azole drugs, available in the market, in human plasma and urine. Moreover, the method was successfully applied for the quantitative determination of two model drugs (itraconazole and miconazole) after oral administration in real samples.
本文报道了一种微萃取-高效液相色谱-二极管阵列检测（MEPS-HPLC-DAD）方法，用于同时测定生物样品中用于治疗不同全身和局部真菌感染的12种唑类药物（联苯苄唑、布康唑、克霉唑、益康唑、伊曲康唑、酮康唑、咪康唑、泊沙康唑、雷夫康唑、特康唑、噻康唑和伏立康唑）。唑类药物在36分钟内完成分离。该分析方法在以下范围内进行了验证：雷夫康唑为0.02 - 5μg/mL；特康唑为0.2 - 5μg/mL；其他化合物为0.05 - 5μg/mL。分析过程中使用人血浆和尿液作为生物样品，同时使用4-羟基苯甲酸苄酯作为内标。精密度（RSD%）和准确性（偏差%）值符合国际指南要求。据我们所知，这是首个与微萃取相结合的HPLC-DAD方法，可同时分析市售的12种唑类药物在人血浆和尿液中的含量。此外，该方法成功应用于实际样品中口服两种模型药物（伊曲康唑和咪康唑）后的定量测定。
