UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用  

Concentration Determination of Voriconazole in Human Plasma by UPLC-MS/MS and Its Clinical Application

作　　者：钟皎[1] 郝琨[2] 裴泽军[1] 

机构地区：[1]无锡市第二人民医院/南京医科大学附属无锡第二医院药剂科,江苏无锡214002 [2]中国药科大学药物代谢动力学重点实验室,南京210009

出　　处：《中国药房》2016年第29期4064-4067,共4页China Pharmacy

基　　金：无锡市医院管理中心医学科研药学项目(No.YGZXY1301)

摘　　要：目的：建立测定人血浆中伏立康唑浓度的方法,并应用于临床。方法：采用超高效液相色谱-串联质谱法测定。以酮康唑为内标,色谱柱为Shim-pack VP-ODS,流动相为水（含1‰甲酸及2 mmol/L乙酸铵）-乙腈,梯度洗脱,流速为0.3 ml/min,柱温为40℃;采用电喷雾离子源,以多反应监测方式进行正离子扫描,用于定量分析的离子对分别为m/z 351.2→282.2（伏立康唑）、m/z532.1→490.2（内标）。结果：伏立康唑血药浓度在1~10 000 ng/ml范围内线性关系良好（r=0.999 5,n=5）,定量下限为1 ng/ml;日内、日间RSD〈10%;方法回收率〉90%（RSD〈8%）,提取回收率〉70%（RSD〈8%）。采用该法检测10例深部真菌感染患者体内伏立康唑的血药浓度为507.33~7 011.24 ng/ml,有3例患者的血药浓度不在推荐治疗浓度范围内。结论：该方法快速、准确、灵敏度高,适用于伏立康唑治疗药物监测。OBJECTIVE ： To develop a method for concentration determination of voriconazole in human plasma and apply it in the clinic. METHODS： UPLC-MS/MS method was adopted. Using ketoeonazole as internal standard, the determination was performed on Shim-pack VP-ODS column with mobile phase consisted of water （containing 1‰ formic acid and 2 mmol/L ammonium acetate）-acetonitrile （gradient elution） at flow rate of 0.3 ml/min and column temperature of 40 ℃.The electrospray ion source, positive ionizing pattern and multiple reaction monitoring were used; the mass transition ion-pairs of voriconazole and internal standard were m/z 351.2→282.2 and m/z 532.1→490.2. RESULTS： The linear range of voriconazole were 1-10 000 ng/ml （r=0.999 5, n= 5）, and the limit of quantitation was 1 ng/ml; RSDs of inter-day and intra-day were all lower than 10% ; method recovery was higher than 90% （RSD〈8%）, and extraction recovery was higher than 70% （RSD〈8%）. The plasma concentrations of voriconazole in 10 patients with invasive fungal infection determined by this method were 507.33-7 011.24 ng/ml, and those of 3 patients were outside the recommended treatment concentration range. CONCLUSIONS： The established method is fast, accurate and sensitive, and can be applied for the therapeutic drug monitoring of voriconazole.

关 键 词：伏立康唑 超高效液相色谱-串联质谱法 血药浓度 治疗药物监测 侵袭性真菌感染 

分 类 号：R917[医药卫生—药物分析学]