【摘要】 目的:建立快速测定人血浆中伏立康唑及其主要代谢物伏立康唑-N-氮氧化物浓度的HPLC-MS/MS方法,用于人体药代动力学研究。方法:以伏立康唑和伏立康唑-N-氮氧化物的D₃同位素为内标,血浆样品经蛋白沉淀后,用Agilent ZORBAX SB-Aq色谱柱（2.1 mm×50 mm,1.8μm）和API 4000质谱仪进行正离子模式电喷雾离子化分析。流速为0.6 mL·min^-1,以甲醇为有机相,0.1%甲酸为水相,按一定程序进行梯度洗脱。结果:伏立康唑和伏立康唑-N-氮氧化物在10.00～8000 ng·mL^-1范围内线性关系良好,该方法的特异性、批内/批间精密度、准确度、介质效应、提取回收率、稳定性和稀释可靠性符合相关要求。结论:建立了一种准确、简便、可靠的HPLC-MS/MS分析方法,成功应用于健康中国人静脉注射4 mg·kg^-1伏立康唑后的药代动力学研究。更多还原

【Abstract】 Objective: To establish an HPLC-MS/MS method for the rapid determination of voriconazole and its main metabolite voriconazole N-oxide in human plasma for the study of voriconazole pharmacokinetics. Methods: With voriconazole-D₃ and voriconazole-D₃ N-oxide as isotopic internal standards, plasma samples were processed by protein precipitation and analyzed by an Agilent ZORBAX SB-Aq column（2.1 mm ×50 mm, 1.8 μm） and an API 4000 MS with positive electro spray ionization. The flow rate was set at 0.6 mL·min^-1. Gradient elution was carried out with the ratio of methanol and 0.1% formic acid varied as scheduled. Results: The calibration curves for both voriconazole and voriconazole N-oxide ranged from 10.0 to 8000 ng·mL^-1 in human plasma. The specificity, intra-/inter-run precisions, accuracy, matrix effects, extraction recoveries, stabilities as well as the dilution integrity of this method met the relevant requirements.The method was verified with two healthy Chinese subjects under single intravenous injection of 4 mg·kg^-1 voriconazole. Conclusions: An accurate, simple and reliable HPLC-MS/MS method has been developed.The developed method can be used for the pharmacokinetic study of voriconazole.更多还原