Analytical Sciences, Chemical Development, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
J Pharm Biomed Anal. 2010 Feb 5;51(3):577-82. doi: 10.1016/j.jpba.2009.09.019. Epub 2009 Sep 24.
Several mass spectrometry (MS) techniques including accurate MS and MS/MS, as well as hydrogen/deuterium (H/D) exchange, were utilized to characterize a pseudo-oxidative reaction by-product (impurity I) in the pharmaceutical synthesis of S-(thiobenzoyl)thioglycolic acid. The negative ion MS/MS data provided complementary structural information to the positive ion MS/MS data. An understanding of the gas-phase Smiles rearrangement upon collision-induced dissociation (CID) in the negative ion MS/MS mode played an important role in structural elucidation of impurity I. The theoretical calculations by density functional theory (DFT) at the B3LYP/6-311G(d,p) level provided insights into the thermochemistry of the Smiles rearrangement reaction. This pseudo-oxidative impurity is proposed to be generated via the base-catalyzed hydrolysis in solution.
几种质谱 (MS) 技术，包括精确 MS 和 MS/MS，以及氢/氘 (H/D) 交换，被用于表征 S-（硫代苯甲酰）硫代甘氨酸药物合成中假氧化反应副产物（杂质 I）。负离子 MS/MS 数据提供了与正离子 MS/MS 数据互补的结构信息。在负离子 MS/MS 模式下，对碰撞诱导解离 (CID) 过程中气相 Smiles 重排的理解对杂质 I 的结构解析起着重要作用。密度泛函理论 (DFT) 的理论计算在 B3LYP/6-311G(d,p) 水平上提供了对 Smiles 重排反应热力学的深入了解。该假氧化杂质被认为是通过溶液中碱催化水解生成的。
