多索茶碱注射液杂质谱研究

目的：研究多索茶碱注射液的杂质谱，鉴定杂质的结构、明确杂质来源及生产工艺间的关系。方法：采用HPLC法，色谱柱为XBridge C₁₈柱（4.6 mm×250 mm，5 μm），以乙腈-磷酸盐缓冲液（pH 5.8）（12：88）为流动相，流速1.0 mL·min^-1，柱温25℃，检测波长273nm，测定多索茶碱注射液有关物质，确定检出杂质，结合酸、碱、氧化、高温、光照破坏试验和工艺分析归属杂质来源，采用UPLC-MS/MS技术确证杂质结构。结果：4家企业生产的多索茶碱注射液共检测出5种杂质，其中杂质1为7-（2'，2'-二羟基）-1，3-二甲基-1H-嘌呤-2，6（3H，7H）-二酮，杂质3为1-（（1，3-二氧戊环-2-基）甲基）-N-甲基-4-（甲基氨基）-1H-咪唑-5-甲酰胺，杂质4为7-（2-羟乙基）-1，3-二甲基-1H-嘌呤-2，6（3H，7H）-二酮，杂质2为茶碱，杂质5为1，3-二甲基-9-（1，3-二氧环戊基-2-基）甲基-3，9-二氢-1H-嘌呤-2，6-二酮。结论：工艺分析结果表明杂质来源，杂质1、3、4为降解杂质，杂质2、5分别为多索茶碱合成起始原料和合成副产物杂质。

Objective: To investigate the impurity profile of doxofylline injection,identify the structures and sources of impurities.Method: HPLC separation of all detected impurities was carried out on a Waters XBridge C₁₈ column(4.6 mm×250 mm,5 μm),with a mobile phase consisting of acetonitrile-phosphate buffer(pH 5.8)(12:88)at a flow rate of 1.0 mL·min^-1,the column temperature was 25℃ and the detection wavelength was 273 nm.The sources of impurities were studied by combining degradation test results and synthesis process.The structures of impurities were identified by UPLC-MS/MS.Result: Five impurities were detected in four pharmaceutical manufacturers.Conclusion: Process analysis showed the source of impurities.Impurity 1,3,4 were degradation impurities and impurity 2,5 were process related substances.

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