Umezawa Hironobu, Lee Xiao-Pen, Arima Yoshiko, Hasegawa Chika, Izawa Hikaru, Kumazawa Takeshi, Sato Keizo
Department of Legal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
Biomed Chromatogr. 2008 Jul;22(7):702-11. doi: 10.1002/bmc.987.
A detailed procedure for the analysis of four beta-blockers, acebutolol, labetalol, metoprolol and propranolol, in human plasma by high-performance liquid chromatography (LC)-tandem mass spectrometry (MS-MS) using an MSpak GF column, which enables direct injection of crude plasma samples, is presented. Protein and/or macromolecule matrix compounds were eluted first from the column, while the drugs were retained on the polymer stationary phase of the MSpak GF column. The analytes retained on the column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. All drugs showed base peak ions due to [M + H]+ ions by LC-MS with positive ion electrospray ionization, and the product ions were produced from each [M + H]+ ion by LC-MS-MS. Quantification was performed by selected reaction monitoring. The recoveries of the four beta-blockers spiked into plasma were 73.5-89.9%. The regression equations for all compounds showed excellent linearity in the range 10-1000 ng/mL of plasma, with the exception of propranolol (10-800 ng/mL). The limits of detection and quantification for each drug were 1-3 and 10 ng/mL, respectively, of plasma. The intra- and inter-day coefficients of variation for all drugs in plasma were not greater than 10.9%.
本文介绍了一种使用MSpak GF柱通过高效液相色谱（LC）-串联质谱（MS-MS）分析人血浆中四种β受体阻滞剂（醋丁洛尔、拉贝洛尔、美托洛尔和普萘洛尔）的详细方法，该方法可直接进样粗血浆样品。蛋白质和/或大分子基质化合物首先从柱上洗脱，而药物则保留在MSpak GF柱的聚合物固定相上。然后使用梯度分离技术将保留在柱上的分析物洗脱到富含乙腈的流动相中。通过LC-MS采用正离子电喷雾电离时，所有药物均显示出由于[M + H]+离子产生的基峰离子，并且通过LC-MS-MS从每个[M + H]+离子产生产物离子。通过选择反应监测进行定量。加入血浆中的四种β受体阻滞剂的回收率为73.5-89.9%。所有化合物的回归方程在血浆浓度范围为10-1000 ng/mL时显示出良好的线性，普萘洛尔除外（10-800 ng/mL）。每种药物在血浆中的检测限和定量限分别为1-3 ng/mL和10 ng/mL。血浆中所有药物的日内和日间变异系数均不大于10.9%。
