1,4-二氢吡啶类钙拮抗剂在超临界色谱中的对映体分离

Enantioseparation of 1,4-dihydropyridines calcium antagonistsby supercritical fluid chromatography

目的:建立超临界流体色谱法手性分离1,4-二氢吡啶类钙拮抗剂(1,4-DHPs),并基于超分子作用机制对其手性识别机理进行初步探讨。方法:采用超临界流体色谱法,以超临界二氧化碳作为流动相,流动相流速2 m L·min^(-1),检测波长237 nm,研究5种1,4-DHPs(尼索地平、西尼地平、普拉地平、阿折地平、盐酸马尼地平)在Sino-Chiral OJ手性色谱柱上的对映体分离,并考察不同改性剂种类(甲醇、乙醇、异丙醇)、比例以及系统背压(13~17 MPa)对分离效果的影响。结果:5种1,4-DHPs在柱温为35℃,系统背压为15 MPa时,在30 min内均实现了基线分离(分离度>1.5),尼索地平、西尼地平、普拉地平、阿折地平、盐酸马尼地平优化改性剂依次为二氧化碳-异丙醇(92∶8)、二氧化碳-甲醇(84∶16)、二氧化碳-乙醇(74∶26)、二氧化碳-乙醇(74∶26)、二氧化碳-乙醇(74∶26)。研究发现,随着改性剂比例的增大,容量因子逐渐减小;甲醇和乙醇对1,4-DHPs的洗脱能力始终大于异丙醇;系统背压越大,出峰速度越快。结论:1,4-DHPs对映体在超临界流体色谱上可得到高效、快速的分离,其识别机理对同类化合物的拆分具有一定指导意义。

Objective： To establish the methods for enantioseparation of five 1,4-dihydropyridinescalcium antagonist （ 1,4-DHPs ） by supercritical fluid chromatography （ SFC ） on chiral stationary phase, and to explore the seperationmechanism based on supermolecular chemistry. Methods： Five 1,4-DHPs （ nisoldipine, cilnidipine, pranidipine, azelnidipine, manidipine hydrochloride ）were separated by supercritical fluid chromatography （ SFC ） with supercritical carbon dioxide on a Sino-Chiral OJ column atthe flow rate of 2 mL＂ rain-1 at the temperature of 35 ~C and the UV detection was set on 237 nm. The effect of different type and percentage of modifiers （ methanol,ethanol, isopropanol ） and back pressure （ 13-17 MPa ） on the separation was also investigated. Results： All the 1,4-DHPs were obtained from the optimal separation （ resolution 〉1.5 ） with the back pressure of 15 MPa and ratioof carbon dioxidide-isopropanol （ 92 ： 8 ）, carbon dioxidide-methanol （ 84 ： 16 ）, carbon dioxidide-ethanol （ 74 ： 26 ）, carbon dioxidide-ethanol （ 74 ： 26 ）, carbon dioxidide-ethanol （ 74 ： 26 ）, respectively. The study found the decrease of capacity factor was with the increase of modifiers＇ percentage, and the higher the back pressure of the system, the faster the peak of the 1,4-DHPs eluted. The elution capacity of both methanol and ethanol was more effective than that of isopropanol. Conclusion. DHPs can be separated by SFC effectively and quickly, and the separation mechanism can be used as guidance for the same kind of compounds.