title: Rapid quantification of miglustat in human plasma and cerebrospinal fluid by liquid chromatography coupled with tandem mass spectrometry.
abstract: 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 microm, 150 mm x 2.1 mm) column, with a mobile phase of acetonitrile/water/ammonium acetate buffer (75/10/15, v/v/v) delivered at 230 microl/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.
authors.affiliation: Laboratoire de ciblage thérapeutique en cancérologie, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, F-69495 Pierre Bénite, France. jerome.guitton@chu-lyon.fr
authors.forename: Jérôme
authors.initials: J
authors.lastname: Guitton
authors.forename: Sylvie
authors.initials: S
authors.lastname: Coste
authors.forename: Nathalie
authors.initials: N
authors.lastname: Guffon-Fouilhoux
authors.forename: Sabine
authors.initials: S
authors.lastname: Cohen
authors.forename: Monique
authors.initials: M
authors.lastname: Manchon
authors.forename: Marc
authors.initials: M
authors.lastname: Guillaumont
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000134:cerebrospinal fluid; D002138:Calibration; D002648:Child; D002853:Chromatography, Liquid; D004355:Drug Stability; D004791:Enzyme Inhibitors / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D016018:Least-Squares Analysis; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D004791:Enzyme Inhibitors; C045621:miglitol; D017485:1-Deoxynojirimycin; C059896:miglustat