LC-MS/MS测定人血浆中阿罗洛尔浓度

Determination of Arotinolol Concentration in Human Plasma by LC-MS/MS

关键词:  阿罗洛尔  液质联用  血药浓度  药动学

Key words:  arotinolol  LC-MS/MS  plasma drug concentration  pharmacokinetics

摘要:

目的 建立LC- MS/MS方法测定人血浆中阿罗洛尔的浓度。方法 人血浆样品用乙酸乙酯提取后，选用ZORBAX Extend C₁₈(2.1 mm×100 mm，3.5 mm)色谱柱，以乙腈-水(80∶20，含0.1%甲酸)为流动相，流速为0.30 mL·min^-1，采用电喷雾离子化源，正离子方式，多反应监测(MRM)扫描方式进行监测，用于定量分析的离子反应分别为m/z372.3→315.9(阿罗洛尔)和m/z 267.2→145.0(内标阿替洛尔)。结果 血浆中阿罗洛尔的线性范围为0.5~1 000 ng·mL^-1(r=0.995 2)，定量下限为0.5 ng·mL^-1；日内、日间RSD均<15%； 低、中、高3 个浓度的提取回收率分别为(80.6±1.6)%，(83.2±3.1)%和(87.5±4.5)%。结论 该方法快速、灵敏、准确，专属性强，重复性好，适用于人血浆中阿罗洛尔浓度的测定，可应用于阿罗洛尔的血药浓度检测和药动学研究。

Abstract:

OBJECTIVE To develop a LC-MS/MS method for determination of arotinolol concentration in human-plasma. METHODS The plasma samples were processed with ethyl acetate extraction and separated on ZORBAX Extend C₁₈ column (2.1 mm×100 mm, 3.5 μm) and eluted with acetonitrile-water (80∶20, containing 0.1% formic acid). Detection of the analyte was achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. The MS/MS ion transitions monitored were m/z 372.3→m/z 315.9 and m/z 267.2→m/z 145.0 for arotinolol and internal standard, respectively. RESULTS The linear calibration curve of arotinolol was obtained concentration range of 0.5-1 000 ng·mL^-1(r=0.995 2), with the lower limit of quantitation of 0.5 ng·mL^-1. Intra-day and inter-day relative standard deviations were both <15%. The recoveries of low, middle and high concentrations were (80.6±1.6)%, (83.2±3.1)% and (87.5±4.5)%, respectively. CONCLUSION The established method is rapid, sensitive, accurate, specific and reliable, and suitable for the determination of arotinolol in human plasma and pharmacokinetic study.