Bioanalysis of (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid (LY379268) in rat plasma using derivatization liquid chromatography/mass spectrometry.

BACKGROUND (1R,4R,5S,6R)-4-amino-2-oxabicyclo[3.1.0]hexane-4,6-dicarboxylic acid, also known as LY379268, a group II metabotropic glutamate receptor agonist, has been widely used in neuroscience as a model compound in studies evaluating antipsychotic drugs for the treatment of schizophrenia. MATERIALS & METHODS So far, no reports describing methods of the bioanalysis of LY379268 have been published. Here, a novel method is presented for determining LY379268 in rat plasma employing precolumn derivatization with pentafluorobenzoyl chloride reagent coupled to liquid chromatography/mass spectrometry. CONCLUSION Chemical derivatization of a low-molecular-weight and highly polar molecule yields a derivative that is retained on a reversed-phase liquid chromatography column with improved tandem mass spectrometric response.

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