CN110455936A - 一种简易的埃索美拉唑钠中间体中cs2的检测方法 - Google Patents

一种简易的埃索美拉唑钠中间体中cs2的检测方法 Download PDF

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CN110455936A
CN110455936A CN201910503961.7A CN201910503961A CN110455936A CN 110455936 A CN110455936 A CN 110455936A CN 201910503961 A CN201910503961 A CN 201910503961A CN 110455936 A CN110455936 A CN 110455936A
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阴启明
吴玉良
杨波勇
赵阳
张照兴
李树谨
王茜
陈玉玺
孙光勇
孙雪莲
伦立军
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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Abstract

本发明公开了一种简易的埃索美拉唑钠中间体中CS2的检测方法，包括如下步骤：供试品溶液：取2‑巯基‑5‑甲氧基苯并咪唑适量，加甲醇溶解并稀释制成每1ml中约含7mg的溶液，对照品溶液：取二硫化碳适量，加甲醇溶解并稀释制成每1ml中约含2.1μg的溶液，通过高效液相色谱仪检测埃索美拉唑钠关键中间体（2‑巯基‑5‑甲氧基苯并咪唑）中的二硫化碳。本发明采用了较为普遍的高效液相色谱技术，该方法在专属性、线性、定量限、检测限、准确度、精密度、稳定性和耐用性等指标上均可达到检测要求，具备较高的检测精准度，符合中国药品监管机构对于药品检测的严格要求，同时该方法降低了检测成本并缩短了物料检测放行时间，适合在商业化生产中应用。

Description

一种简易的埃索美拉唑钠中间体中CS2的检测方法
技术领域
本发明涉及药学技术领域，具体为一种简易的埃索美拉唑钠中间体中CS2的检测方法。
背景技术
埃索美拉唑钠(下式所示)是奥美拉唑的S-旋光异构体的钠盐，是全球首个异构体质子泵抑制剂(PPI)，通过特异性抑制胃壁细胞质子泵减少胃酸分泌。经大量临床实验和药物研究证实：其维持胃内pH>4 的时间更长，抑酸效率更高，疗效优于前两代PPI，个体差异小。作为新一代PPI，现已广泛应用于临床治疗诸多酸相关疾病。
合成埃索美拉唑钠的关键中间体为2-巯基-5-甲氧基苯并咪唑，在制备2-巯基-5-甲氧基苯并咪唑的过程中使用到了二硫化碳作为环合试剂，因此在2-巯基-5-甲氧基苯并咪唑的质量标准和检测项目中，二硫化碳的残留和检测势必作为一个必检项。
由于二硫化碳作为一种特殊控制的化学试剂，其化学结构和控制限度决定了其检测方法通常需要采用气相色谱与火焰光度检测器(FPD检测器)或者采用灵敏度更高的GC-MS等方法检测，而上述方法检测成本较高，方法开发较复杂，特别是质谱检测在后续大生产样品中的应用会产生较高的检测费用和较长的检测周期，不适合商业化生产。
发明内容
发明的目的在于提供一种简易的埃索美拉唑钠中间体中CS2的检测方法，该方法在专属性、线性、定量限、检测限、准确度、精密度、稳定性和耐用性等指标上均可达到检测要求，具备较高的检测精准度，符合中国药品监管机构对于药品检测的严格要求，同时该方法降低了检测成本并缩短了物料检测放行时间，适合在商业化生产中应用，以解决上述背景技术中提出的问题。
一种简易的埃索美拉唑钠中间体中CS2的检测方法，包括如下步骤：
步骤1：供试品溶液：取2-巯基-5-甲氧基苯并咪唑适量，加甲醇溶解并稀释制成每1ml中约含7mg的溶液；
步骤2：对照品溶液：取二硫化碳适量，加甲醇溶解并稀释制成每1ml中约含2.1μg的溶液；
步骤3：通过高效液相色谱仪检测埃索美拉唑钠关键中间体(2- 巯基-5-甲氧基苯并咪唑)中的二硫化碳。
进一步地，所使用的色谱柱为C18色谱柱，Agela Venusil XBP C18(4.6mm×250mm，5μm)。
进一步地，所使用的流动相：0.1％四丁基氢氧化铵溶液(用磷酸调节pH值至7.0)-乙腈(40∶60)。
进一步地，所使用的检测波长：315nm。
进一步地，所使用的流速：1.0ml/min。
进一步地，所使用的柱温：30℃。
与现有技术相比，本发明的有益效果是：本发明提出的简易的埃索美拉唑钠中间体中CS2的检测方法，本发明采用了较为普遍的高效液相色谱技术，该方法在专属性、线性、定量限、检测限、准确度、精密度、稳定性和耐用性等指标上均可达到检测要求，具备较高的检测精准度，符合中国药品监管机构对于药品检测的严格要求，同时该方法降低了检测成本并缩短了物料检测放行时间，适合在商业化生产中应用。
具体实施方式
以下将详细说明本发明实施例，然而，本发明实施例并不以此为限。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
本发明实施例中：一种简易的埃索美拉唑钠中间体中CS2的检测方法，包括：
仪器：LC-20A高效液相色谱仪
色谱柱：C18，Agela Venusil XBP C18(4.6mm×250mm，5μm)
流动相：0.1％四丁基氢氧化铵溶液(用磷酸调节pH值至7.0)- 乙腈(40∶60)
检测波长：315nm
流速：1.0ml/min
柱温：30℃。
供试品溶液：取2-巯基-5-甲氧基苯并咪唑适量，加甲醇溶解并稀释制成每1ml中约含7mg的溶液。
对照品溶液：取二硫化碳适量，加甲醇溶解并稀释制成每1ml中约含2.1μg的溶液。
通过高效液相色谱仪检测埃索美拉唑钠关键中间体(2-巯基-5- 甲氧基苯并咪唑)中的二硫化碳。
本发明的方法学验证总结如下表：
综上所述，本发明提出的简易的埃索美拉唑钠中间体中CS2的检测方法，本发明采用了较为普遍的高效液相色谱技术，该方法在专属性、线性、定量限、检测限、准确度、精密度、稳定性和耐用性等指标上均可达到检测要求，具备较高的检测精准度，符合中国药品监管机构对于药品检测的严格要求，同时该方法降低了检测成本并缩短了物料检测放行时间，适合在商业化生产中应用。
尽管已经示出和描述了本发明的实施例，对于本领域的普通技术人员而言，可以理解在不脱离本发明的原理和精神的情况下可以对这些实施例进行多种变化、修改、替换和变型，本发明的范围由所附权利要求及其等同物限定。

Claims (6)

1.一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，包括如下步骤：
步骤1：供试品溶液：取2-巯基-5-甲氧基苯并咪唑适量，加甲醇溶解并稀释制成每1ml中约含7mg的溶液；
步骤2：对照品溶液：取二硫化碳适量，加甲醇溶解并稀释制成每1ml中约含2.1μg的溶液；
步骤3：通过高效液相色谱仪检测埃索美拉唑钠关键中间体（2-巯基-5-甲氧基苯并咪唑）中的二硫化碳。
2.根据权利要求1所述的一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，所使用的色谱柱为C18色谱柱，Agela Venusil XBP C18（4.6mm×250mm，5μm）。
3.根据权利要求1所述的一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，所使用的流动相：0.1%四丁基氢氧化铵溶液（用磷酸调节pH值至7.0）-乙腈（40∶60）。
4.根据权利要求1所述的一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，所使用的检测波长：315nm。
5.根据权利要求1所述的一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，所使用的流速：1.0ml/min。
6.根据权利要求1所述的一种简易的埃索美拉唑钠中间体中CS2的检测方法，其特征在于，所使用的柱温：30℃。
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