固相萃取结合HPLC-MS测定人血浆中奥美沙坦的药物质量浓度

 目的建立人血浆中奥美沙坦质量浓度的HPLC-MS测定法。方法血浆样品用OASIS HLB 3cc固相萃取小柱萃取,在Diamonsil C₁₈(4.6 mm×150 mm,5μm)色谱柱上分离,流动相为甲醇-水(含体积分数为0.2%醋酸)(70∶30),流速0.5 mL·min^-1。LC-ESI/MS选择离子检测,正离子模式,用于定量分析的离子分别为m/z 447.2(奥美沙坦),m/z515.3(内标,替米沙坦)。结果奥美沙坦血药质量浓度在1～3 000μg·L^-1内的线性关系良好(r=0.999 9),血浆中低、中、高3种质量浓度(3,100,2 400μg·L^-1)的相对回收率在97.6%～100.9%之间,日内RSD≤5.2%,日间RSD≤13.3%。结论本法操作简便、准确、灵敏,适用于临床药动学研究。

Quantitative Analysis of Olmesartan in Human Plasma by HPLC-MS With Solid-Phase Extraction

OBJECTIVE To develop a sensitive and specific HPLCMS method for the quantitative analysis of omlesartan in human plasma.METHODS The plasma sample was extracted by Waters OASIS HLB 3cc solid-phase extraction mini column,then separated on a Diamonsil C₁₈(4.6 mm×150 mm,5 μm)analytical column.The mobile phase consisted of methanol-water(contaning 0.2% acetic acid)(70∶30) at a flow rate of 0.5 mL·min^-1.A mass spectrometer equpied with electrospray ionization source was used as detector and operated in the positive ion mode.In selected ion monitoring(SIM)mode,the ion of m/z 447.2 and m/z 515.3 was used to qualify olmesartan and internal standard(telmisartan),respectively.RESULTS Chromatograms showed no endogenous peaks with the respective blank human plasma samples.The linearity was obtained in the concentration range of 1～3 000 μg·L^-1,and the limit of quantitativation was 1 μg·L^-1.The relative recoveries of low,medium and high concentration were within 97.6%～100.9%.The intra-day and inter-day RSDs were less than 5.2% and 13.3%,respectively.CONCLUSION The method is simple,accurate,sensitive,and suitable for clinical investigation of olmesartan medoxomil pharmacokinetics.