篇名: UPLC-MS/MS法测定人血浆中伏立康唑的浓度及其临床应用
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/z 532.1→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。
ABSTRACT: 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 ketoconazole 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.
期刊: 2016年第27卷第29期
作者: 钟皎,郝琨,裴泽军
关键字: 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
KEYWORDS: Voriconazole; UPLC-MS/MS; Plasma concentration; Therapeutic drug monitoring; Invasive fungal infection
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