title: Evaluation of deuterium isotope effects in normal-phase LC-MS-MS separations using a molecular modeling approach.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298-0533, USA.
authors.forename: Sunil S
authors.initials: SS
authors.lastname: Iyer
authors.forename: Zong-Ping
authors.initials: ZP
authors.lastname: Zhang
authors.forename: Glen E
authors.initials: GE
authors.lastname: Kellogg
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Karnes