LC-MS法测定人血浆中比索洛尔的浓度

目的: 建立高效液相色谱-质谱联用法测定人血浆中比索洛尔浓度的方法,并研究富马酸比索洛尔片剂在健康人体的药代动力学。 方法: 血浆样品以阿奇霉素作为内标,经2 mol·L^-1氢氧化钠溶液0.1 mL碱化后乙酸乙酯萃取进行LC-MS分析。色谱条件为Kromasil C₁₈柱(150 mm×4.6 mm,5 μm),流动相为甲醇-0.2%甲酸(55∶ 45,v/v),流速0.8 mL·min^-1;质谱条件为电喷雾离子源(ESI源),正离子方式检测:扫描方式为选择离子监测(SIM),用于定量分析的离子分别为m/z 326.25(比索洛尔)和m/z 749.80(阿奇霉素)。 结果: 比索洛尔浓度在0.2 ~ 150.0 ng·mL^-1范围内线性关系良好,方法的定量下限(LLOQ)为0.2 ng·mL^-1,日内、日间精密度(RSD)均小于13.2%,提取回收率在95.2% ~ 98.2%之间。 结论: 该方法简便、准确,灵敏度高,专属性强,适用于人血浆中比索洛尔浓度的测定。

Objective: To develop an LC-MS method for the determination of bisoprolol concentration in human plasma and study the pharmacokinetics of bisoprolol in healthy volunteers after a single oral dose of 5 mg bisoprolol fumarate tablet preparation. Method: After adding azithromycin as the internal standard and 0.1 mL 2 mol·L^-1NaOH as the basification reagent,bisoprolol was extracted from plasma by ethyl acetate and the separation was carried on a Kromasil C₁₈ column (150 mm×4.6 mm,5 μm)with a mobile phase of methanol-0.2% formic acid(55∶ 45) at a flow rate of 0.8 mL·min^-1.Bisoprolol was determined by LC-ESI/MS in selected ion monitoring(SIM) mode,the ion combination of m/z 326.25 and m/z 749.80 was used to qualify bisoprolol and the internal standard,respectively. Result: The calibration curve was in good linearity over the range of 0.2-150.0 ng·mL^-1.The lower limit of quantification(LLOQ) for bisoprolol in plasma was 0.2 ng·mL^-1.The intra-day and inter-day precision (RSD) were lower than 13.2%.The recovery for bisoprolol was between 95.2%-98.2%. Conclusion: The method is shown to be simple,accurate,sensitive and specific for the determination of bisoprolol in human plasma.