纤维素衍生物手性固定相拆分肾上腺素、盐酸去氧肾上腺素

目的: 采用2种纤维素衍生物手性固定相,比较并建立了肾上腺素、盐酸去氧肾上腺素对映体的拆分分析方法并探讨其机理。 方法: 色谱柱为CHIRALCEL OD-H和CHIRALCEL OJ-H (250 mm×4.6 mm,5 μm);流动相:正己烷-异丙醇(含不同比例甲醇、三氟乙酸、二乙胺);检测波长:280 nm;流速:0.8mL·min^-1;柱温:25℃。同时,考察了有机添加剂酸和碱的比例、醇置换剂的类型和比例及温度对上述化合物分离的影响,同时对分离机理进行了阐述。 结果: 肾上腺素在纤维素衍生物手性固定相正相条件下分离度为1.56,盐酸去氧肾上腺素分离度为2.30。对映体的色谱保留和分离度通过改变流动相中醇类置换剂的浓度、有机改性剂酸和碱的浓度、柱温、流速等因素调节。分离度随醇置换剂浓度减小或流速的降低而增加,有机改性剂酸和碱的浓度分别为0.1%、0.05%,分离度峰形好,样品在柱温25℃时分离度最好,并保持温度不变,以得到稳定的分离结果。 结论: 肾上腺素、盐酸去氧肾上腺素两种药物在纤维素衍生物手性固定相上能得到良好分离。此种分析方法准确快速、灵敏,操作简单。

Objective: To establish and compare methods for the chiral separation of adrenaline and phenylephrine hydrochloride on chiral stationary phases of two cellulose ramifications and explore the method mechanism. Methods: Two cellulose ramification chiral columns of CHIRALCEL OD-H and CHIRALCEL OJ-H were applied.N-hexane and isopropanol (containing different ratios of methanol,trifluoroacetic acid and diethylamine) were applied as the mobile phrase.The flow rate,column temperature and UV detection wavelength were set at 0.8 mL·min^-1,25℃ and 280 nm, respectively.Meanwhile,the effects of proportion of organic additives (i.e,acid and base),the type and proportion of the alcohol displacer,and temperature on the separation were studied,and the mechanism of separation was expounded. Results: The results indicated that adrenaline and phenylephrine hydrochloride could be separated on chiral stationary phase of cellulose ramification in normal phase chromatographic system,and the resolution values were 1.56 and 2.30,respectively.The chromatographic retention and resolution of enantiomers could be adjusted through factors including the concentration of alcohol displacer in mobile phase,the concentration of organic acidic and alkaline modifier,column temperature,and flow rate.It was shown that the resolution was increased with the reducing of alcohol displacer concentration or the reducing of flow rate.When concentration of organic acidic and alkaline modifier was 0.1% and 0.05%,respectively,the peak profile of the resolutionwas fairly good.Adrenaline and phenylephrine hydrochloride had bestresolution at the column temperature of 25℃.The column temperature was maintained stable to obtain stable separation results. Conclusion: Adrenaline and phenylephrine hydrochloride could be well separated by cellulose ramification chiral stationary phase.The analytical method is accurate,rapid,sensitive,and easy to operate.