Department of Pharmaceutical Chemistry, University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania.
Department of Drugs Industry and Pharmaceutical Management, University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Târgu Mureș, Romania.
Electrophoresis. 2019 Nov;40(21):2799-2805. doi: 10.1002/elps.201900107. Epub 2019 Jul 16.
Novel capillary electrophoresis methods using CDs as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors. Fourteen different neutral and anionic CDs were screened at pH 4 and 7 in the preliminary analysis. Sulfobutyl-ether-β-CD with a degree of substitution of 6.5 and 10 at neutral pH proved to be the most suitable chiral selector for both compounds. Various dual CD systems were also compared, and the possible mechanisms of enantiomer separation were investigated. A dual selector system containing sulfobutyl-ether-β-CD degree of substitution 6.5 and native γ-CD proved to be the most adequate system for the separations. Method optimization was carried out using an experimental design approach, performing an initial fractional factorial screening design, followed by a central composite design to establish the optimal analytical conditions. The optimized methods (25 mM phosphate buffer, pH 7, 10 mM sulfobutyl-ether-β-CD/20 mM γ-CD, +20 kV voltage; 17°C temperature; 50 mbar/3 s injection, detection at 210 nm for lansoprazole; 25 mM phosphate buffer, pH 7, 15 mM sulfobutyl-ether-β-CD/30 mM γ-CD, +20 kV voltage; 18°C temperature; 50 mbar/3 s injection, detection at 210 nm for rabeprazole) provided baseline separation for lansoprazole (R = 2.91) and rabeprazole (R = 2.53) enantiomers with favorable migration order (in both cases the S-enantiomers migrates first). The optimized methods were validated according to current guidelines and proved to be reliable, linear, precise, and accurate for the determination of 0.15% distomer as chiral impurity in dexlansoprazole and dexrabeprazole samples.
开发并验证了使用 CD 作为手性选择剂的新型毛细管电泳方法，用于质子泵抑制剂兰索拉唑和雷贝拉唑对映体的手性分离。在初步分析中，在 pH 4 和 7 下筛选了 14 种不同的中性和阴离子 CD。在中性 pH 下，取代度为 6.5 和 10 的磺丁基醚-β-CD 被证明是这两种化合物最适合的手性选择剂。还比较了各种双 CD 系统，并研究了对映体分离的可能机制。含有磺丁基醚-β-CD 取代度为 6.5 和天然 γ-CD 的双选择剂系统被证明是分离的最适当系统。使用实验设计方法进行方法优化，首先进行初步部分因子筛选设计，然后进行中心组合设计以建立最佳分析条件。优化方法（25 mM 磷酸盐缓冲液，pH 7，10 mM 磺丁基醚-β-CD/20 mM γ-CD，+20 kV 电压；17°C 温度；50 mbar/3 s 进样，兰索拉唑检测波长 210nm；25 mM 磷酸盐缓冲液，pH 7，15 mM 磺丁基醚-β-CD/30 mM γ-CD，+20 kV 电压；18°C 温度；50 mbar/3 s 进样，雷贝拉唑检测波长 210nm）为兰索拉唑（R = 2.91）和雷贝拉唑（R = 2.53）对映体提供了基线分离，迁移顺序良好（在这两种情况下，S-对映体先迁移）。根据当前指南验证了优化方法，证明其对于测定右旋兰索拉唑和右旋雷贝拉唑样品中 0.15%对映异构体作为手性杂质是可靠、线性、精确和准确的。
