手性毛细管气相色谱法拆分4-氯甲基-2,2-二甲基-1,3-二氧戊环对映异构体  

Chiral capillary gas chromatography for the separation of the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane

作　　者：张振永 ZHANG Zhenyong(Shimadzu(Shanghai)Global Laboratory Consumables Co.,Ltd.,Shanghai 200233,China)

机构地区：[1]岛津(上海)实验器材有限公司,上海200233

出　　处：《色谱》2023年第12期1135-1140,共6页Chinese Journal of Chromatography

摘　　要：手性化合物具有独特的生物活性,其在药物治疗中发挥着关键作用。为准确测定对映异构体中不同构型的纯度,建立手性化合物对映体分离方法十分关键。4-氯甲基-2,2-二甲基-1,3-二氧戊环是一种重要的手性医药中间体,本文建立了一种手性毛细管气相色谱拆分测定4-氯甲基-2,2-二甲基-1,3-二氧戊环对映异构体的方法。采用固定相为环糊精衍生物的色谱柱Rt-bDEXse进行分离,并以氢火焰离子化检测器进行检测。经过优化,得到最优色谱条件:线速度为70 cm/s;升温程序为初始柱温70℃保持1 min,以2.0℃/min的速率升温到150℃;溶样溶剂为甲醇。实验结果表明,在该条件下,(R)-4-氯甲基-2,2-二甲基-1,3-二氧戊环和(S)-4-氯甲基-2,2-二甲基-1,3-二氧戊环可在10 min内快速分离,两者的分离度远大于1.5,在0.5~50.0 mg/L的范围内线性关系良好,线性相关系数均大于0.998,(R)-和(S)-4-氯甲基-2,2-二甲基-1,3-二氧戊环的检出限分别为0.07和0.08 mg/L,定量限分别为0.22 mg/L和0.25 mg/L。以甲醇作为空白样品,进行0.5、2.0、10.0 mg/L 3个不同水平的加标回收试验,(R)-和(S)-4-氯甲基-2,2-二甲基-1,3-二氧戊环的回收率分别为94.0%~99.1%和96.0%~98.8%,相对标准偏差(RSD)分别为1.26%~4.87%和1.51%~4.46%。该方法可为手性医药中间体4-氯甲基-2,2-二甲基-1,3-二氧戊环对映异构体的拆分提供参考。Chiral compounds play an important role in the pharmaceutical industry owing to their unique biological activities.The enantiomers must be separated because they can exhibit different pharmacological activities.Thus,the development of chiral separation methods is essential to determine the purity of enantiomers.4-Chloromethyl-2,2-dimethyl-1,3-dioxolane is an important chiral pharmaceutical intermediate.In this context,a method based on chiral capillary gas chromatography was established for the separation and determination of the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane.The separation of(R)-and(S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was initially investigated using two conventional stationary-phase capillary columns:SH-I-5Sil MS and SH-WAX.The stationary phase of SH-I-5Sil MS consisted of 5%phenyl and 95%polymethylsiloxane,whereas the stationary phase of SH-WAX consisted of 100%crosslinked polyethylene glycol.Neither of the columns exhibited chiral selectivity,so they both were unable to separate the enantiomers of 4-chloromethyl-2,2-dimethyl-1,3-dioxolane.Subsequently,the separation of(R)-and(S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane was investigated using four chiral columns:Rt-bDEXm,Rt-bDEXsm,Rt-bDEXse,and InertCap CHIRAMIX.Among the chiral columns,Rt-bDEXse,which used a stationary phase composed of 2,3-di-O-ethyl-6-O-tert-butyl dimethylsilylβ-cyclodextrin added to 14%cyanopropyl phenyl and 86%dimethyl polysiloxane,achieved the best separation of(R)-and(S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane.Thus,this column was selected as the analytical column for further method optimization.Detection was performed using a hydrogen flame ionization detector.The effects of various gas chromatographic parameters,such as linear velocity,initial column temperature,column heating rate,and solvent type,on the separation of(R)-and(S)-4-chloromethyl-2,2-dimethyl-1,3-dioxolane were investigated.The optimal chromatographic conditions included a linear velocity of 70 cm/s,an initial column temperature of

关 键 词：气相色谱法 手性拆分 4-氯甲基-2 2-二甲基-1 3-二氧戊环 对映异构体 

分 类 号：O658[理学—分析化学]