Evaluation of deuterium isotope effects in normal-phase LC-MS-MS separations using a molecular modeling approach
Evaluation of deuterium isotope effects in normal-phase LC-MS-MS separations using a molecular modeling approach
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DOI：
10.1093/chromsci/42.7.383
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发表时间：
2004-08-01
影响因子：
1.3
通讯作者：
Karnes, HT
中科院分区：
文献类型：
--
作者：
Iyer, SS;Zhang, ZP;Karnes, HT
固定相的分子模型提出了一个独特的挑战，因为很少有可用的实验推导的结构信息。在分子水平上与分析物验证的相互作用机制也很少见。利用Tripos力场进行分子力学计算，定性和定量地评估固定相相互作用。结果表明，奥氮平（OLZ）、OLZ- d3、去甲基奥氮平（DES）和DES- d8的结合能值分别为- 15.40、15.28、- 12.53和- 12.34 kcal/mol，对应于液相色谱-质谱联用(MS)-MS观察到的四种化合物的保留行为。该模型半定量地解释了这些化合物正相色谱分离中的氘同位素效应。
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-D8that 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.