Premium
Development of analytical methods for the quantification of metabolites of lesogaberan in a MIST investigation
Author(s) -
Dunér Kristina,
Bottner Pernilla,
Norlén AnnaKarin
Publication year - 2014
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.3029
Subject(s) - chemistry , chromatography , protein precipitation , electrospray ionization , metabolite , electrospray , mass spectrometry , tandem mass spectrometry , quantitative analysis (chemistry) , biochemistry
Analytical methods were developed for the determination of six metabolites of lesogaberan to be used in quantitative determinations of metabolites according to the guidelines of Metabolites in Safety Testing. The γ ‐amino butyric acid type B receptor agonist lesogaberan and its metabolites are small polar molecules and hydrophilic interaction liquid chromatography was found to be a suitable separation mode. The samples were prepared using protein precipitation and negative electrospray ionization tandem mass spectrometry was used for detection. Initially, exploratory methods for six metabolites were set up for analysis of human plasma samples taken after repeated administration of a high oral dose of lesogaberan. The purpose was to establish which metabolites were present at concentrations significant for further investigation. Four of the six metabolites were then found at clearly detectable concentrations. The analytical methods for these four metabolites were further elaborated and then taken through a qualification procedure, which showed acceptable accuracy (86–114%), precision (<9%) and good linearity in the range 0.03–5 µmol/L. No interferences were seen from endogenous plasma components. Copyright © 2013 John Wiley & Sons, Ltd.