| 引用本文: | 张拥军,梁紫琦,郭拥政,朱勇华,周文武,王书芳.卡泊芬净及其杂质的LC-QTOF-MS定性分析[J].中国现代应用药学,2023,40(23):3281-3287. |
| ZHANG Yongjun,LIANG Ziqi,GUO Yongzheng,ZHU Yonghua,ZHOU Wenwu,WANG Shufang.Qualitative Analysis of Caspofungin and Its Impurities by LC-QTOF-MS[J].Chin J Mod Appl Pharm(中国现代应用药学),2023,40(23):3281-3287. |
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| 卡泊芬净及其杂质的LC-QTOF-MS定性分析 |
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张拥军1, 梁紫琦2, 郭拥政1, 朱勇华1, 周文武1, 王书芳2,3
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1.浙江野风药业股份有限公司, 浙江 东阳 322100;2.浙江大学金华研究院转化药学创制中心, 浙江 金华 321016;3.浙江大学药学院, 杭州 310058
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| 摘要: |
| 目的 采用LC-QTOF-MS分析醋酸卡泊芬净原料药及其强降解产物的杂质，研究卡泊芬净及其相关杂质(杂质A、B、C、D和E)的质谱特征。方法 采用Waters CORTECS® C18+(4.6 mm×150 mm，2.7 μm)色谱柱，流动相A为0.1%甲酸-水溶液，流动相B为0.1%甲酸-乙腈，流速为0.6 mL·min-1，梯度洗脱；ESI-QTOF-MS正离子扫描检测。结果 在一级质谱中，除杂质D主要显示单电荷准分子离子峰外，卡泊芬净及其余4个杂质均以多电荷准分子离子峰的响应较高；在二级质谱中，卡泊芬净及其他含乙二胺结构的杂质均会丢失乙二胺及其所连基团产生碎片离子m/z 103 3；卡泊芬净及其相关杂质主要通过肽键的断裂生成一系列碎片离子，也可以通过丢失氨基酸残基中的羟基、酰基或氨基生成碎片离子；杂质A和杂质C分别显示高丰度的特征碎片离子m/z 137.070 8和m/z 77.071 1，可以与卡泊芬净及其他杂质区分。结论 卡泊芬净及其5个杂质均具有明显的质谱特征，研究结果可为卡泊芬净生产过程中可能出现的未知杂质的结构鉴定提供参考，以便及早发现生产工艺中的潜在问题，降低产品质量风险。 |
| 关键词: 卡泊芬净 杂质 LC-QTOF-MS 定性分析 |
| DOI：10.13748/j.cnki.issn1007-7693.20231407 |
| 分类号:R917.101 |
| 基金项目: |
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| Qualitative Analysis of Caspofungin and Its Impurities by LC-QTOF-MS |
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ZHANG Yongjun1, LIANG Ziqi2, GUO Yongzheng1, ZHU Yonghua1, ZHOU Wenwu1, WANG Shufang2,3
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1.Zhejiang Wild Wind Pharmaceutical Co., Ltd., Dongyang 322100, China;2.Innovation Center of Translational Pharmacy, Jinhua Institute of Zhejiang University, Jinhua 321016, China;3.College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
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| Abstract: |
| OBJECTIVE To analyze caspofungin acetate and the samples under different strong degradation conditions by LC-QTOF-MS, and to study the characteristics in mass spectra of caspofungin and its related impurities(impurities A, B, C, D and E). METHODS Chromatographic separation was accomplished on Waters CORTECS® C18+(4.6 mm×150 mm, 2.7 μm) column using a gradient elution with monile phase of 0.1% formic acid-H2O(A) and 0.1% formic acid-CH3CN(B) at a flow velocity of 0.6 mL·min-1; The analytes was detected in positive ion scan mode by ESI-QTOF-MS. RESULTS In MS1 spectra, except that impurity D mainly showed single-charge quasi-molecular ion, caspofungin and the other four impurities showed muti-charge quasi-molecular ions with high abundance; In MS2 spectra, caspofungin and its impurities that containing ethylenediamine generated fragment ions at m/z 1 033 by losing the ethylenediamine and the groups attached to it; caspofungin and its impurities produced a series of fragment ions mainly through the cleavage of peptide bonds, as well as through the loss of hydroxyl, acyl, or amino groups from amino acid residues; Impurity A and C showed characteristic fragment ions m/z 137.070 8 and m/z 77.071 1 with high abundance, respectively, which could be used to distinguish them from caspofungin and the other impurities. CONCLUSION Caspofungin and its five impurities have distict characteristics in their mass spectra. The research results can provide reference for identifying the structures of unknown impurities that may occur in the production process of caspofungin, so as to quickly discover the potential problems in the production process and reduce the quality risk of the products. |
| Key words: caspofungin impurity LC-QTOF-MS qualitative analysis |
