Department of Chemistry, Laser Chemistry Institute, Fudan University, Shanghai, 200438, China.
Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Provincial, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China.
Rapid Commun Mass Spectrom. 2021 Apr 30;35(8):e9052. doi: 10.1002/rcm.9052.
Rationale The rapid identification of small-molecule chiral drugs is challenging due to subtle structural differences. Different enantiomers of chiral drugs may produce inverse biological effects through their different pharmacokinetics. Therefore, it is highly desirable to distinguish the chirality of drug molecules.
The chirality of pregabalin was distinguished by studying the ion mobility spectra of the ternary non-covalent complexes formed with cyclodextrins (CDs), pregabalin, and alkali-earth cations using trapped ion mobility spectrometry (TIMS). The ternary non-covalent complex ions were determined by electrospray ionization of mixed solutions. The analyzed sample was simply mixed, without derivatization or sample pretreatment. The relative contents of pregabalin enantiomers were derived using a calibration curve method.
The ion mobility spectra of several ternary non-covalent complexes formed with α-, β-, and γ-CD, pregabalin, and alkali-earth cations were obtained. We compared their ability to distinguish the chirality of pregabalin. The best peak-to-peak resolution (R ) was estimated to be 2.20 for [2β-CD + pregabalin + Sr] , which can be ascribed as baseline separation. The derived relative contents for S-pregabalin were in agreement with the actual contents.
A novel and convenient method for discriminating the chirality of the pregabalin molecule by TIMS was developed and optimized. The chirality of pregabalin was recognized by studying the ion mobility spectra of the ternary non-covalent complexes, such as [2β-CD + pregabalin + Sr] . This TIMS method could also be used to quantify the relative contents of pregabalin enantiomers.
由于结构细微差异，快速识别小分子手性药物具有挑战性。手性药物的不同对映异构体可能通过不同的药代动力学产生相反的生物学效应。因此，区分药物分子的手性非常重要。
采用离子淌度谱法（TIMS），通过研究环糊精（CD）、普瑞巴林和碱土金属阳离子形成的三元非共价复合物的离子淌度谱，区分普瑞巴林的手性。通过混合溶液的电喷雾电离来确定三元非共价复合物离子。分析样品只需简单混合，无需衍生化或样品预处理。使用校准曲线法得出普瑞巴林对映体的相对含量。
获得了几种与 α-、β-和 γ-CD、普瑞巴林和碱土金属阳离子形成的三元非共价复合物的离子淌度谱。我们比较了它们区分普瑞巴林手性的能力。[2β-CD+普瑞巴林+Sr]+的最佳峰-峰分辨率（R）估计为 2.20，可视为基线分离。得出的 S-普瑞巴林的相对含量与实际含量一致。
开发并优化了一种通过 TIMS 区分普瑞巴林分子手性的新颖简便方法。通过研究三元非共价复合物（如[2β-CD+普瑞巴林+Sr]+）的离子淌度谱来识别普瑞巴林的手性。该 TIMS 方法还可用于定量普瑞巴林对映体的相对含量。
