Department of Chemistry, Virginia Tech, Blacksburg, VA, USA.
Department of Chemistry, Chromatography and Mass Spectroscopy Center, Virginia Tech, Blacksburg, VA, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Aug 15;1092:279-285. doi: 10.1016/j.jchromb.2018.06.019. Epub 2018 Jun 15.
The enantiomeric separation of a racemate of 7-oxa-bicyclo[2.2.1]heptene sulfonate (OBHS) derivatives, a Selective Estrogen Receptor Modulator (SERM), was obtained using supercritical fluid chromatography in tandem with UV and mass spectrometry (SFC/UV and SFC/MS, respectively). Supercritical CO modified with methanol or isopropyl alcohol was used with isopropylamine (IPAm), trimethylamine (TEA), or trifluoroacetic acid (TFA) as an additive to obtain the enantiomers separations. Both Chiralpak IC and IA were evaluated for the separation of enantiomers. Results showed enantiomers separation can be achieved in less than 5 min with a resolution greater than 1 and 0.9, respectively, for the different OBHS derivatives (compounds A and B) using supercritical CO modified with 40% isopropyl alcohol containing 0.25% IPAm and IC column applying isocratic conditions. Similar conditions were used with the semi-preparative Chiralpak IC column to isolate more than 50 mg of each enantiomer. SFC/MS and SFC/UV results showed pure enantiomers were isolated. Method development via SFC was much simpler than those reported in the literature using HPLC.
使用超临界流体色谱与紫外和质谱联用（分别为 SFC/UV 和 SFC/MS），对 7-氧杂双环[2.2.1]庚烯磺酸酯（OBHS）衍生物的外消旋体（一种选择性雌激素受体调节剂[SERM]）进行对映体拆分。使用甲醇或异丙醇改性的超临界 CO2，并添加异丙胺（IPAm）、三甲胺（TEA）或三氟乙酸（TFA）作为添加剂，以获得对映体分离。分别评估了 Chiralpak IC 和 IA 对拆分对映异构体的性能。结果表明，使用改性超临界 CO2（含 40%异丙醇和 0.25% IPAm）在 IC 柱上应用等度条件，对于不同的 OBHS 衍生物（化合物 A 和 B），可以在不到 5 min 内实现对映异构体分离，分离度分别大于 1 和 0.9。使用半制备型 Chiralpak IC 柱，可分离出每种对映异构体 50 毫克以上。SFC/MS 和 SFC/UV 结果表明分离得到了纯对映异构体。与文献中报道的使用 HPLC 的方法相比，SFC 的方法开发要简单得多。
