Frigerio E, Pianezzola E, Strolin Benedetti M
Farmitalia Carlo Erba, Pharmacokinetics and Metabolism Department, Milan, Italy.
J Chromatogr A. 1994 Feb 4;660(1-2):351-8. doi: 10.1016/0021-9673(94)85130-1.
A sensitive and selective high-performance liquid chromatographic method for the determination of reboxetine enantiomers in human plasma was developed. Although two chiral centres are present in reboxetine, its stereospecific synthesis leads to two rather than four possible enantiomers. After extraction from plasma and reaction with (+)-1-(9-fluorenyl)ethyl chloroformate, reboxetine enantiomers were separated as diastereoisomeric derivatives by reversed-phase high-performance liquid chromatography (HPLC) and determined by fluorimetric detection. The HPLC analysis time was about 90 min. The linearity, precision, accuracy and limit of quantification of the method were evaluated. No interference from blank plasma sample was observed. The suitability of the method for in vivo samples was assessed by the analysis of plasma samples obtained from a healthy male volunteer who had received a single oral dose of 4 mg of reboxetine in tablet form.
建立了一种灵敏且具选择性的高效液相色谱法，用于测定人血浆中的瑞波西汀对映体。尽管瑞波西汀存在两个手性中心，但其立体定向合成产生的是两种而非四种可能的对映体。从血浆中提取并与（+）-1-（9-芴基）乙基氯甲酸酯反应后，瑞波西汀对映体通过反相高效液相色谱（HPLC）分离为非对映异构体衍生物，并通过荧光检测进行测定。HPLC分析时间约为90分钟。对该方法的线性、精密度、准确度和定量限进行了评估。未观察到空白血浆样品的干扰。通过分析来自一名健康男性志愿者的血浆样品来评估该方法对体内样品的适用性，该志愿者口服了4mg片剂形式的瑞波西汀单剂量。
