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目的建立快捷的高效液相色谱-串联质谱法(HPLC-MS/MS)测定某院侵袭性真菌感染患者血浆中伏立康唑的谷浓度,并初步考察其有效谷浓度范围。方法以氯雷他定为内标,用乙腈直接蛋白沉淀的方法,色谱柱为ZORBAX Eclipse XDB-C18柱(50 mm×4.6 mm,1.8μm),流动相为乙腈—0.1%甲酸的10 mmol·L~(-1)甲酸铵水溶液(85∶15),流速为0.4 mL·min~(-1),正离子多反应监测(MRM)模式扫描分析,检测15例侵袭性真菌感染患者的伏立康唑谷浓度,并观察其临床疗效和不良反应。结果血浆中伏立康唑浓度的线性范围为0.01~10.00μg·m L~(-1)(r=0.999 2),定量下限为0.01μg·mL~(-1),提取回收率在94.94%~104.73%之间,日内、日间精密度相对标准偏差(RSD)均小于15%。患者体内伏立康唑的血药浓度为0.739~8.763μg·mL~(-1)。结论该方法快速、灵敏,适用于伏立康唑血药浓度监测。由于伏立康唑的个体间浓度差异大,对危重患者开展常规伏立康唑谷浓度监测有助于提高临床疗效,减少不良反应的发生。
OBJECTIVE To establish a rapid HPLC-MS / MS method for the determination of voriconazole in plasma of patients with invasive fungal infection in a hospital and to investigate the effective trough concentration range. Methods The method was as follows: using loratadine as internal standard and precipitating with acetonitrile directly on a ZORBAX Eclipse XDB-C18 column (50 mm × 4.6 mm, 1.8 μm) with a mobile phase of 10 mmol ·· -1 of acetonitrile and 0.1% formic acid (-1) ammonium formate solution (85:15), the flow rate was 0.4 mL · min -1, and the positive ion MRM mode was used for scanning analysis. The Vriconazole valley in 15 patients with invasive fungal infection was detected. Concentration, and observe its clinical efficacy and adverse reactions. Results The linear range of voriconazole in plasma was 0.01-10.00 μg · mL -1 (r = 0.999 2), the lower limit of quantitation was 0.01 μg · mL -1, the recovery was 94.94% -104.73% The relative standard deviations (RSDs) of intra-day and inter-day precision were less than 15%. The blood concentration of voriconazole in patients was 0.739 ~ 8.763μg · mL ~ (-1). Conclusion The method is rapid and sensitive and suitable for voriconazole plasma concentration monitoring. Due to the large differences in the individual concentrations of voriconazole, routine vorconazole trough concentrations monitoring in critically ill patients can help to improve the clinical efficacy and reduce the incidence of adverse reactions.