Evaluation of Deuterium Isotope Effects in Normal-Phase LC-MS-MS Separations Using a Molecular Modeling Approach.

Molecular modeling of stationary phases presents a unique challenge because there is little available experimentally derived structural information. Verified interaction mechanisms at a molecular level with analytes are also rare. Molecular mechanics calculations using the Tripos force field were carried out to qualitatively and quantitatively assess stationary phase interactions. Binding energy values of –15.40, 15.28, –12.53, and –12.34 kcal/mol, respectively, are obtained for olanzapine (OLZ), OLZ-D3, des-methyl olanzapine (DES), and DES-D8 that corresponded to the retention behavior of the four compounds observed using liquid chromatography–mass spectrometry (MS)–MS. The model explains, semiquantitatively, the deuterium isotope effect in the normal-phase chromatographic separation of these compounds. [ABSTRACT FROM AUTHOR]