Rapid quantification of miglustat in human plasma and cerebrospinal fluid by liquid chromatography coupled with tandem mass spectrometry

Autor: Jérôme Guitton, Sabine Cohen, Sylvie Coste, Marc Guillaumont, Nathalie Guffon-Fouilhoux, M. Manchon
Rok vydání: 2009
Předmět:
Zdroj: Journal of Chromatography B. 877:149-154
ISSN: 1570-0232
Popis: Miglustat (OGT 918) is an iminosugar recently introduced in therapeutic as potential alternative therapy in disorders found in several diseases such as Tay-Sachs, Gaucher or Niemann-Pick diseases. A highly sensitive liquid-chromatography–electrospray tandem mass spectrometry (LC–MS/MS) assay was developed for the quantification of miglustat in human plasma and cerebrospinal fluid (CSF). The sample preparation consists in a simple protein precipitation with a mixture of acetonitrile/methanol (75/25) which yields 100% recovery. The isocratic separation utilizes an Atlantis Hilic (3 μm, 150 mm × 2.1 mm) column, with a mobile phase of acetonitrile/water/ammonium acetate buffer (75/10/15, v/v/v) delivered at 230 μl/min. Selected reaction monitoring (SRM) mode was used with the transitions m/z 220 → 158 for the miglustat and m/z 208 → m/z 146 for the miglitol (internal standard). Good linearity was observed in a range from 125 to 2500 ng/ml and from 50 to 1000 ng/ml, for plasma and CSF, respectively. The within-run precision of the assay was less than 6%, and the between-run run precision was less than 6.5%, for six replicates at each of three concentrations and evaluated on three separated days for both plasma and CSF mediums. Assay accuracy was in the range of 98–106.5%. Stability of miglustat was reported under a variety of storage conditions. The miglustat concentrations in two children are presented to demonstrate the clinical interest of this new method.
Databáze: OpenAIRE