Rapid quantification of miglustat in human plasma and cerebrospinal fluid by liquid chromatography coupled with tandem mass spectrometry.
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.
Guitton
Jérôme
J
Laboratoire de ciblage thérapeutique en cancérologie, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, F-69495 Pierre Bénite, France. jerome.guitton@chu-lyon.fr
Coste
Sylvie
S
Guffon-Fouilhoux
Nathalie
N
Cohen
Sabine
S
Manchon
Monique
M
Guillaumont
Marc
M
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
D004791:Enzyme Inhibitors; C045621:miglitol; D017485:1-Deoxynojirimycin; C059896:miglustat