Labat Laurence, Goncalves Antonio, Marques Ana Rita, Duretz Bénédicte, Granger Bernard, Declèves Xavier
Biologie du Médicament et Toxicologie, Groupe Cochin (Assistance Publique - Hôpitaux de Paris), France.
Inserm UMR - S1144 Universités (Paris Descartes - Paris Diderot), France.
Biomed Chromatogr. 2017 Aug;31(8). doi: 10.1002/bmc.3936. Epub 2017 Feb 17.
Baclofen is used to manage alcohol dependence. This study describes a simple method using liquid chromatography coupled to high-resolution mass spectrometry (LC-HR-MS) developed in plasma samples. This method was optimized to allow quantification of baclofen and determination of metabolic ratio of its metabolites, an oxidative deaminated metabolite of baclofen (M1) and its glucuronide form (M2). The LC-HR-MS method on Exactive® apparatus is a newly developed method with all the advantages of high resolution in full-scan mode for the quantification of baclofen and detection of its metabolites in plasma. The present assay provides a protein precipitation method starting with 100 μL plasma giving a wide polynomial dynamic range (R > 0.999) between 10 and 2000 ng/mL and a lower limit of quantitation of 3 ng/mL for baclofen. Intra- and inter-day precisions were <8.1% and accuracies were between 91.2 and 103.3% for baclofen. No matrix effect was observed. The assay was successfully applied to 36 patients following baclofen administration. Plasma concentrations of baclofen were determined between 12.2 and 1399.9 ng/mL and metabolic ratios were estimated between 0.4 and 81.8% for M1 metabolite and on the order of 0.3% for M2 in two samples.
巴氯芬用于治疗酒精依赖。本研究描述了一种在血浆样本中使用液相色谱-高分辨率质谱联用（LC-HR-MS）的简单方法。该方法经过优化，可对巴氯芬进行定量，并测定其代谢物的代谢率，巴氯芬的氧化脱氨基代谢物（M1）及其葡萄糖醛酸苷形式（M2）。在Exactive®仪器上的LC-HR-MS方法是一种新开发的方法，具有全扫描模式下高分辨率的所有优点，可用于血浆中巴氯芬的定量及其代谢物的检测。本测定提供了一种蛋白质沉淀方法，以100μL血浆开始，在10至2000 ng/mL之间具有宽的多项式动态范围（R＞0.999），巴氯芬的定量下限为3 ng/mL。巴氯芬的日内和日间精密度＜8.1%，准确度在91.2%至103.3%之间。未观察到基质效应。该测定成功应用于36例服用巴氯芬的患者。巴氯芬的血浆浓度在12.2至1399.9 ng/mL之间测定，M1代谢物的代谢率在0.4%至81.8%之间估计，两个样本中M2的代谢率约为0.3%。
