Application to therapeutic drug monitoring.Laurence Labat, Antonio Goncalves, Ana Rita Marques, Bénédicte Duretz,
Bernard Granger and Xavier Declèves
Abstract
Baclofen is actually 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 new developed method with all the
advantages of the 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 (R2 > 0.999)
between 10 and 2000 ng/mL and a LLOQ of 3 ng/mL for baclofen. Intra- and inter-day
precisions were below 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 in the order of 0.3% for M2 in two samples.
