【作者】 廖日房； 温预关； 曾转萍； 李国成； 伍俊妍；

【Author】 Rifang Liao~a,Yuguan Wen~b,Zhuanping Zeng~c,Guocheng Li~a,Junyan Wu~a a. Department of pharmacy,The Second Affiliated Hospital of Sun Yat-sen University,Guangzhou 510120,China; b. Department of Clinical Pharmacology,Guangzhou Brain Hospital,Guangzhou 510370,China; c. Department of Eepidemiology,Public Health College,Guangdong Pharmacy University,Guangzhou 510310,China;

【机构】 中山大学附属第二医院药学部； 广州市脑科医院临床药理研究所； 广东药学院公卫学院；

【摘要】 目的建立测定人血浆中米力农浓度的LC-ESI-MS/MS方法。方法血浆样品用二氯甲烷: 乙酸乙酯(4:1, v/v)提取,在37 oC真空干燥箱中干燥至干,残渣用200 mL流动相溶解后进样。色谱条件为:色谱柱为Agilent Eclipse XDB-C18 (4.6 mm × 150 mm,5 ìm); 流动相为乙腈(含1%甲酸): 4 mmol·L–1醋酸铵(80:20,V/V),流速为0.8 mL·min–1。质谱条件:采用美国安捷仑1200 高效液相色谱系统和安捷仑6410三级杆串联质谱仪, 质谱条件为电喷雾离子源,检测方式为正离子电离、多离子反应监测(MRM),用于定量分析的离子为米力农m/z 212→140。结果该方法应用于检测10名健康志愿者服药后的血浆样品。线性范围为0.5 ~1000 ng·mL–1(r = 0.997), 日内和日间精密度均低于8.7%,提取回收率为77.0–79.3%。最低检测限为0.5 ng·mL-1 (S/N>20)。结论该方法灵敏、准确、快速,可用于该药药代动力学和生物等效性研究。更多还原

【Abstract】 Aim A rapid and sensitive liquid chromatography–tandem mass spectrometry (LC/MS/MS) method to determine milrinone in human plasma was developed and fully validated. Methods After ethyl acetate-dichloromethane (4:1, v/v) induced extraction from the plasma samples, milrinone was subjected to LC/MS/MS analysis using electro-spray ionization. Chromatography was performed on a C18 column. Results The extraction recoveries of milrinone were found to be 77.0–79.3%. Milrinone was stable under routine laboratory conditions. A minimal matrix effect resulting in a slight ionization suppression of milrinone (<10.8%) was observed, which did not markedly affect the behavior of the calibrations curves and accuracy and precision data. The method had a chromatographic run time of 2 min and a linear calibration curve over the concentration range 0.5–1000 ng/mL for milrinone. The lower limit of quantification (LLOQ) of the method was 0.5 ng/mL(S/N>20). The intra- and inter-day precision was less than 8.7%. Conclusion These results indicated that this LC/MS/MS method has high selectivity and efficiency, and acceptable accuracy, precision and sensitivity. The validated LC/MS/MS method has been successfully used in a pharmacokinetic study in healthy volunteers treated with a single intravenous injection of milrinone at 50μg/kg and 75μg/kg.更多还原