两种原料药及一种医药中间体中异构体杂质的HPLC分析方法研究

发布时间：2018-08-25 07:23

【摘要】：手性药物具有含量高、疗效好、副作用小等优点,受到医生和患者的广泛青睐。手性固定相高效液相色谱法是目前最成熟的色谱分离技术方法之一,因其分离效率高、操作简便而被广泛应用。本文采用手性固定相技术,通过考察色谱柱类型、流动相配比、流速和柱温对分离效果的影响,开发了拆分原料药右旋酮洛芬氨丁三醇、盐酸阿托莫西汀及中间体N-甲基帕罗西汀中对映体杂质的高效液相色谱分析方法,具体结果如下:1、开发了基于DAICEL OJ-RH色谱柱的手性分离右旋酮洛芬氨丁三醇中对映体杂质的高效液相色谱法。结果表明,最佳的流动相为正己烷:异丙醇:乙酸(9:1:0.03),流速为1.0 mL/min,柱温为30℃。该方法的定量限为0.243μg/mL,在0.243~30.3μg/mL的浓度范围内相关系数R~2=1,回收率在92.8~115.7%,RSD为3.6%。2、开发了基于CHIRALCEL OD-H色谱柱的手性分离盐酸阿托莫西汀中对映体杂质的高效液相色谱法。结果表明,最佳的流动相为正己烷:异丙醇:二乙胺(85:15:0.2),流速为1.0 mL/min,柱温为30℃。该方法的定量限为1μg/mL,在0.90~1.5μg/mL的浓度范围内相关系数R~2=0.9983,回收率在86.3~112.8%,RSD为0.9%。3、开发了基于CHIRALPAK AD-H色谱柱的手性分离N-甲基帕罗西汀中对映体杂质的高效液相色谱法。结果表明,最佳的流动相为正己烷:乙醇:水:三氟乙酸(900:105:2:1.95),流速为1.0 mL/min,柱温为25℃。该方法的定量限为2.5μg/mL,在2.5~38μg/mL的浓度范围内相关系数R~2=0.9909,回收率在109.5~115.6%,RSD为0.8%。
[Abstract]:Chiral drugs have the advantages of high content, good curative effect and little side effect, so they are widely favored by doctors and patients. Chiral stationary phase high performance liquid chromatography (HPLC) is one of the most mature chromatographic separation techniques and has been widely used because of its high separation efficiency and simple operation. The chiral stationary phase technique was used to study the effects of chromatographic column type, mobile phase ratio, flow rate and column temperature on the separation effect. Determination of enantiomers in atomoxetine hydrochloride and its intermediate N-methylparoxetine by high performance liquid chromatography. The results are as follows: 1. The chiral separation of enantiomers from dextoprofen amitriol based on DAICEL OJ-RH column has been developed by high performance liquid chromatography (HPLC). The results showed that the best mobile phase was n-hexane: isopropanol: acetic acid (9: 1: 0.03), the flow rate was 1.0 mL/min, and the column temperature was 30 鈩，

本文编号：2202160