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Separation of stereoisomers of 7-oxa-bicyclo[2.2.1]heptene sulfonate (OBHS), a Selective Estrogen Receptor Modulator (SERM), via chiral stationary phases using SFC/UV and SFC/MS
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2018-06-15 , DOI: 10.1016/j.jchromb.2018.06.019
Penagaluri Balasubramanyam , Mehdi Ashraf-Khorassani , Jatinder S. Josan

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 CO2 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 CO2 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.



中文翻译:

使用SFC / UV和SFC / MS通过手性固定相分离7-氧杂双环[2.2.1]庚烯磺酸盐(OBHS),一种选择性雌激素受体调节剂(SERM)的立体异构体

使用超临界流体色谱与紫外光谱和质谱联用(SFC / UV),获得了7-氧杂双环[2.2.1]庚烯磺酸盐(OBHS)的外消旋物(一种选择性雌激素受体调节剂(SERM))的对映体分离。和SFC / MS)。将经甲醇或异丙醇改性的超临界CO 2与异丙胺(IPAm),三甲胺(TEA)或三氟乙酸(TFA)用作添加剂,以获得对映体分离。对Chiralpak IC和IA都评估了对映体的分离。结果表明,使用超临界CO 2对不同的OBHS衍生物(化合物A和B),对映体分离可以在不到5分钟的时间内完成,分离度分别大于1和0.9。用含0.25%IPAm的40%异丙醇和应用等度条件的IC色谱柱改性。半制备型Chiralpak IC色谱柱使用相似的条件,以分离出50 mg以上的每种对映异构体。SFC / MS和SFC / UV结果表明已分离出纯对映体。通过SFC进行的方法开发比文献中使用HPLC报道的方法简单得多。

更新日期:2018-06-15
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