建立了正相高效液相色谱法分离托法替布及其光学异构体，并定量测定其对映异构体和非对映异构体。采用Chiralpak AS-H 手性柱，以正己烷∶乙醇∶甲醇∶乙醇胺(70 ∶ 20 ∶ 10 ∶ 0.2) 为流动相，检测波长290 nm。托法替布及其光学异构体均分离完全。3R,4S- 型、3S,4R- 型非对映异构体和3S,4S- 型对映异构体分别在0.6 ～ 12、0.6 ～ 12 和0.5 ～ 10 μg/ml 范围内线性关系良好 ；平均回收率分别为100.8％、98.8％和98.6％，RSD 分别为1.21％、1.34％和1.61％。
Abstract
An NP-HPLC method was established for the chiral separation of tofacitinib and its optical isomers, as well as the determination of the enantiomer and diastereoisomers. A Chiralpak AS-H column was used, with the mobile phase of hexane∶ethanol∶methanol∶2-aminoethanol (70∶20∶10∶0.2) at the detection wavelength of 290 nm. Tofacitinib and its optical isomers could be separated completely. Their were linear for the (3R,4S)- and (3S,4R)- diastereoisomers and (3S,4S)- enantiomer in the ranges of 0.6—12, 0.6—12 and 0.5—10 μg/ml, respectively. The average recoveries of diastereoisomers and enantiomer were 100.8％, 98.8％ and 98.6％, with RSDs of 1.21％, 1.34％ and 1.61％, respectively.
关键词
枸橼酸托法替布 /
对映异构体 /
非对映异构体 /
手性拆分 /
高效液相色谱 /
测定
{{custom_keyword}} /
Key words
tofacitinib citrate /
enantiomer /
diastereoisomer /
chiral separation /
HPLC /
determination
{{custom_keyword}} /
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] 张建忠. 2012 年11 月FDA 批准新药概况[J]. 上海医药,2013, 34(1): 61.
[2] 郭宗儒. 化学生物学与药物化学研发托伐替尼[J]. 药学学报, 2014, 49(2): 282—284.
[3] 王燕娇, 刘永进, 郭文敏, 等. 枸橼酸托法替布中的四种光学异构体的HPLC 法测定[J] . 中国医药工业杂志, 2015,46(9): 2007—2009.
[4] Kasat RB, Wang NH, Franses EI. Experimental probing and modeling of key sorbent-solute interactions of norephedrine enantiomers with polysaccharide-based chiral stationary
phases [J]. J Chromatogr A, 2008, 1190(1-2): 110—119.
[5] Stringham RW, Ye YK. Chiral separation of amines by highperformance liquid chromatography using polysaccharide stationary phases and acidic additives [J]. J Chromatogr A,
2006, 1101(1-2): 86—93.
[6] Cai WL, Colony JL, Frost H, et al. Investigation of practical routes for the kilogram-scale production of cis-3- methylamino-4-methylpiperidines [J]. Org Process Res Dev, 2005, 9: 51—56.
[7] Patil YS, Bonde NL, Kekan AS, et al. An improved and efficient process for the preparation of tofacitinib citrate [J]. Org Process Res Dev, 2014, 18(12): 1714—1720.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
