Horai Y, Ishizaki T, Kusaka M, Tsujimoto G, Hashimoto K
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Ther Drug Monit. 1988;10(4):428-33. doi: 10.1097/00007691-198804000-00009.
A simple, sensitive, and highly reliable liquid chromatographic method using fluorescence detection is described for the simultaneous determination of metoprolol and alpha-hydroxymetoprolol in plasma and urine. This method involves a single extraction of the compounds with the internal standard pindolol from alkalinized plasma or urine into dichloromethane. A reconstituted aliquot with a mobile phase is injected onto a reversed-phase, Zorbax ODS column, and the detection is achieved by the excitation and emission wavelengths at 230 and 300 nm, respectively. The assay is reproducible and precise for metoprolol and alpha-hydroxymetoprolol in both plasma and urine samples, as judged by a coefficient of variation of less than 9.2% at all concentrations examined. The standard curves for metoprolol and alpha-hydroxymetoprolol are linear over 10-200 ng/ml in plasma and over 0.5-10 micrograms/ml in urine. The lower detection limit is 2 ng/ml for each of the compounds in plasma using a 0.5-ml sample. Preliminary data on the oxidation polymorphism of metoprolol in Japanese subjects are reported using the current assay method. In 183 Japanese subjects no poor metabolizer of metoprolol has been identified so far.
本文描述了一种使用荧光检测的简单、灵敏且高度可靠的液相色谱法，用于同时测定血浆和尿液中的美托洛尔和α-羟基美托洛尔。该方法包括用内标品吲哚洛尔从碱化的血浆或尿液中单次提取化合物，提取液用二氯甲烷萃取。将用流动相复溶的一份样品注入反相Zorbax ODS柱，分别通过230和300 nm的激发波长和发射波长进行检测。在所有检测浓度下，变异系数均小于9.2%，表明该方法对血浆和尿液样品中的美托洛尔和α-羟基美托洛尔具有可重复性和精密度。美托洛尔和α-羟基美托洛尔的标准曲线在血浆中10 - 200 ng/ml范围内以及尿液中0.5 - 10 μg/ml范围内呈线性。使用0.5 ml样品时，血浆中每种化合物的最低检测限为2 ng/ml。本文使用当前的检测方法报告了日本受试者中美托洛尔氧化多态性的初步数据。在183名日本受试者中，目前尚未发现美托洛尔的慢代谢者。
