高效液相色谱-质谱联用法测定人血浆中洛伐他汀的浓度

Determination of lovastatin concentration in human plasma by high performance liquid chromatography-electrospray mass spectrometry

目的:建立高效液相色谱质谱联用法测定人血浆中洛伐他汀的浓度。方法:色谱条件———色谱柱为DiamonsilC18(150mm×2.1mm,5μm),流动相为乙腈∶水=60∶40,流速为0.4mL·min-1,柱温40℃;质谱条件———电喷雾离子化法(ESI)采集正离子,单离子方式检测洛伐他汀m/z405和内标辛伐他汀m/z419。血浆样品预处理采用环己烷二氯甲烷(3∶1)萃取法。结果:方法的线性范围为0.5～50μg·L-1,r=0.9989,检测限为0.1μg·L-1,标准血浆样品0.5,4,20μg·L-1的日内和日间精密度为RSD<14.47%,方法回收率为88.12%～112.09%,提取回收率为76.28%～77.15%。结论:该法灵敏、专属,适用于洛伐他汀人体药动学的研究。

AIM： To develop a high-performance liquid chromatography-mass spectrometry （HPLC-MS） method for the determination of lovastatin concentration in human plasma. METHODS： The chromatographic separation was performed on a Diamonsil C18 column （5 μm, 2.1 mm×150 mm） at 40℃. The mobile phase, a mixture of acetonitrile： water （60 ： 40）, was delivered at a flow-rate of 0.4 mL·min^-1. MS detection in single ion monitoring mode （SIM） using electrospray ionization （ESI） as an interface was applied to determine positive ions at m/z 405 for lovastatin and m/z 419 for internal standard （IS, simvastatin）. Lovastatin and IS were isolated by a liquid-liquid extraction using cyclohexane： methylene dichloride （3 ： 1） as the solvent. RESULTS： High specificity and a low quantitation limit （0.1 μg·L^-1） were achieved. Linearity was confirmed in the concentration range of 0.5-50 μg·L^-1 with the correlation coefficient （r） = 0.998 9. The relative standard deviation （RSD） values of intra- and inter-day assay were less than 14.47 % and the recoveries were within 88.12 %-112.09 %. The extraction recovery of lovastatin was ranged from 76.28 % to 77.15 %. CONCLUSION： HPLC-MS method is sensitive, specific and applicable to pharmacokinetic studies of lovastatin in human.