CN115248262A - 一种缬沙坦及对映异构体的分离检测方法 - Google Patents
一种缬沙坦及对映异构体的分离检测方法 Download PDFInfo
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Abstract
本发明提供了一种缬沙坦及对映异构体的分离检测方法,属于药物分析领域。采用纤维素类涂覆型手型色谱柱,以正相混合溶剂为流动相对缬沙坦及对映异构体,能有效的分离并准确测定缬沙坦及对映异构体。本发明方法简便,灵敏度高,分离度、重现性好,结果准确可靠,可用于缬沙坦对映异构体的检测。
Description
技术领域
本发明属于药物分析技术领域,一种缬沙坦及对映异构体的高效液相色谱分离检测方法。
背景技术
缬沙坦是一款血管紧张素II受体拮抗剂抗高血压类药物,该药物是起到使血管紧张素II的I型(AT1)受体封闭,血管紧张素II血浆水平升高,刺激未封闭的AT2受体,同时抗衡AT1受体的作用,从而达到扩张血管降低血压的效果,主要用于治疗高血压。化学名称为:N-戊酰基-N-[[2′-(1H-四氮唑-5-基)联苯-4-基]甲基]-L-缬氨酸,其化学结构式如下:
缬沙坦存在一个手性中心,根据缬沙坦的合成工艺路线及合成中所使用的起始物料,可知,本品的合成路线中存在对映异构体。
因对映异构体很难在普通的高效液相色谱上进行分离,因此开发缬沙坦的对映异构体检测方法,检测和分离出缬沙坦对映异构体,可以保证缬沙坦产品的有效性和安全性。
对于制备缬沙坦过程中产生的异构体,不论是在原料药还是制剂中均需要进行严格控制。目前中国药典中收载有缬沙坦,并且有对映异构体检测方法,但是中国药典中缬沙坦对映异构体检测方法,采用的色谱柱酸性糖蛋白柱,色谱柱由于蛋白质容易变性失活,故在使用时,对有机相的种类和浓度的选择都有一定的限制,且在使用时色谱柱维护比较麻烦。
因此需要开发简单可行、灵敏度高、专属性好的缬沙坦及对映异构体分析检测方法,用于缬沙坦的质量控制,对于实现对缬沙坦的安全性保证具有极其重要的意义。
发明内容
本发明针对背景技术中的不足,提供了一种缬沙坦对映异构体的检测方法,具有简便、高效和准确度高等优点,可准确反映缬沙坦原料药中对映异构体的含量,从而能够更好地控制和掌握产品质量,并提高临床用药的安全性。
本发明采用以下技术方案:
本发明提供了一种有效分离缬沙坦及其对映异构体的高效液相色谱检测方法。所述方法包括:照高效液相色谱法测定,用淀粉-3,5-二甲苯基氨基甲酸酯键衍生物为填充剂,以正己烷-异丙醇为流动相,在一定条件下进行等度洗脱。
在一个优选的实施例中,色谱柱采用CHIRALPAK IA(4.6mm×250mm,5μm)。
在一个优选的实施例中,所述流动相正己烷-异丙醇的体积比为90~96∶10~4,更优选94∶6。
在一个优选的实施例中,柱温:33℃~37℃,更优选35℃。
在一个优选的实施例中,0.8mL/min~1.2mL/min,更优选1.0mL/min。
在一个优选的实施例中,检测器采用紫外检测器,检测波长227nm
本发明还提供一种测定缬沙坦对映异构体的含量的高效液相方法,包括以下步骤:
(1)系统适用性溶液配制:精密称取缬沙坦对照品、对映异构体对照品,分别用无水乙醇稀释制成每1ml含缬沙坦约1mg、对映异构体1μg,作为系统适用性溶液;
样品溶液配制:取缬沙坦待测样品,用无水乙醇配制成浓度为0.8mg~1.2mg/m1的溶液,作为供试品溶液;
(2)色谱条件
色谱柱填充剂:淀粉-3,5-二甲苯基氨基甲酸酯键衍生物
柱温:33℃~37℃
流速:0.8mL/min~1.2mL/min
检测波长:227nm
流动相:己烷-异丙醇的体积比为90~96∶10~4
(3)将所述系统适用性溶液、供试品溶液按照所述(2)色谱条件依次进样,记录色谱图,按照面积归一化法计算缬沙坦对映异构体含量。
本发明所述的缬沙坦对映异构体的检测方法能够使缬沙坦与其对映异构体有效分离,分离度≥1.5,保证检测的有效性,能够准确严格地控制缬沙坦的质量,该方法专属性强,灵敏度高,准确度与耐用性良好。
具体实施方式
为对本发明进行详细说明,下面结合具体实施例做进一步说明,以下实施例仅用于说明本发明,并不限制本发明的保护范围。
附图说明
图1为实施例1中溶剂的高效液相色谱图
图2为实施例1中系统适用性溶液的高效液相色谱图。
图3为实施例1中缬沙坦供试品溶液的高效液相色谱图。
实施例1:专属性试验
采用本发明中的方法。
色谱柱:CHIRALPAK IA(4.6mm×250mm,5μm)
流动相:正己烷-异丙醇的体积比为94∶16
流速:1.0ml/min
柱温:35℃
检测波长:227nm
进样体积:20μl
实验步骤:
空白溶剂:无水乙醇
系统适用性溶液配制:精密称取缬沙坦对照品、对映异构体对照品,分别用无水乙醇液稀释制成每1ml含缬沙坦约1mg、对映异构体1μg,作为系统适用性溶液;
样品溶液配制:取本品适量,精密称定,置量瓶中,用无水乙醇溶解并稀释制成1mg/ml的溶液。
取上述各溶液,分别注入高效液相色谱仪,记录色谱图。
空白溶剂的结果见附图1。
系统适用性溶液的结果见附图2。
样品溶液的结果见附图3。
结果:空白溶剂不干扰缬沙坦及其对映异构体的检测,该方法专属性良好。附图2中从左往右峰依次为对映异构体和缬沙坦,其分离度为5.90,大于1.5,能够达到基线分离。
实施例2:回收率试验
采用实施例1中的色谱方法。
实验步骤:
精密称取缬沙坦适量,置量瓶中,精密加入缬沙坦对映异构体贮备液适量,用无水乙醇溶解并稀释至刻度,配制成相对浓度分别为50%、100%、150%的溶液,摇匀,作为供试品溶液。每个浓度平行制备3份。另精密称定缬沙坦适量,用乙醇溶解并稀释至刻度,摇匀,作为空白样品溶液。另精密量取缬沙坦对映异构体贮备液适量,用无水乙醇定量稀释制成合适浓度的溶液,作为对照品溶液。精密量取上述溶液各20μl,分别注入液相色谱仪,记录色谱图及峰面积。计算回收率。
结果:各浓度下缬沙坦对映异构体的回收率均符合药典规定,本方法准确度良好,具体数据见下表:
缬沙坦对映异构体回收率结果
在限度值50%浓度,限度值100%浓度,限度150%浓度下的加样回收率分别为:缬沙坦对映异构体为88.1%~100.3%,结果表明本方法准确度良好。
实施例3:本发明方法的耐用性试验
通过改变流速、柱温、流动相比例等参数来考察测试方法的耐受性。每次测试仅改变其中一个参数,其结果与不改变参数时所测结果进行比较。对映异构体和缬沙坦的分离度均不小于1.5,符合要求。具体结果见下表:
实施例4样品检测试验
1、仪器与条件:
高效液相色谱仪:Thermofisher Dixonex U3000型,紫外检测器
色谱柱:淀粉-3,5-二甲苯基氨基甲酸酯键衍生物CHIRALPAK IA(4.6mm×250mm,5μm)
流动相:正己烷-异丙醇的体积比为94∶6
流速:1.0ml/min
柱温:35℃
进样体积:20μl
检测波长:227nm
2、实验方法和结果
稀释液:乙醇
系统适用性溶液配制:精密称取缬沙坦对照品、对映异构体对照品,分别用稀释液液稀释制成每1ml含缬沙坦约1mg、对映异构体1μg,作为系统适用性溶液;
样品溶液配制:取缬沙坦待测样品,用稀释液配制成浓度为1.0mg/ml的溶液,作为供试品溶液;取上述溶液各20μl,依次注入液相色谱仪,并记录色谱图。
表4缬沙坦异构体检测实验结果
批号 | 对映异构体 |
XST-190203 | 未检出 |
XST-190402 | 未检出 |
XST-190502 | 未检出 |
Claims (7)
1.一种缬沙坦对映异构体的分离检测方法,特征在于:采用硅胶表面涂覆有淀粉-3,5-二甲苯基氨基甲酸酯键衍生物为填料,流动相为正相混合溶剂为正己烷-异丙醇,在一定条件下进行等度洗脱。
2.如权利要求1要求所述的缬沙坦对映异构体的分离检测方法,其特征在于:所述色谱柱为CHIRALPAK IA(4.6mm×250mm,5μm)。
3.如权利要求1所述的缬沙坦对映异构体的分离检测方法,其特征在于:所述流动相正己烷-异丙醇的体积比为90~96∶10~4。
4.如权利要求3所述的缬沙坦对映异构体的分离检测方法,其特征在于:正己烷-异丙醇的体积比为94∶6。
5.如权利要求1要求所述的缬沙坦对映异构体的分离检测方法,其特征在于:流动相流速为0.8~1.2ml/min;色谱柱温度为33~37℃;检测器采用紫外检测器,检测波长为227nm。
6.如权利要求5要求所述的缬沙坦对映异构体的检测方法,其特征在于:所述流动相流速为1.0ml/min;所述色谱柱温度为35℃。
7.一种缬沙坦对映异构体的含量检测方法,其特征在于包括以下步骤:
(1)系统适用性溶液配制:精密称取缬沙坦对照品、对映异构体对照品,分别用无水乙醇稀释制成每1ml含缬沙坦约1mg、对映异构体1μg,作为系统适用性溶液;
样品溶液配制:取缬沙坦待测样品,用无水乙醇配制成浓度为0.8mg~1.2mg/ml的溶液,作为供试品溶液;
(2)色谱条件
色谱柱填充剂:淀粉-3,5-二甲苯基氨基甲酸酯键衍生物
柱温:33℃~37℃
流速:0.8mL/min~1.2mL/min
检测波长:227nm
流动相:己烷-异丙醇的体积比为90~96∶10~4
(3)将所述系统适用性溶液、供试品溶液按照所述(2)色谱条件依次进样,记录色谱图,按照面积归一化法计算缬沙坦对映异构体含量。
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