摘要
目的优化长春西汀注射液中有关物质的测定方法,并研究其杂质谱,明确杂质来源及其与生产工艺间的关系。方法采用HPLC法,色谱柱为ACE Excel C_(18)柱(4.6 mm×250 mm,5μm),以乙腈-0.2 mol·L^(-1)乙酸铵溶液为流动相,梯度洗脱,流速1.0 mL·min^(-1),柱温35℃,检测波长280 nm,测定7家企业生产的79批次长春西汀注射液中有关物质,采用UHPLC-Q-TOF对最大未知杂质结构进行推测,结合酸、碱、氧化、高温和氧化破坏试验及工艺分析和模拟灭菌工艺,确定检出杂质,归属杂质来源。结果优化后的检测方法,可对长春西汀杂质A、B、C、D、F及长春胺、苯甲醛和糠醛等8个已知杂质进行有效分离和测定。7家企业生产的长春西汀注射液均检出3~6种已知杂质和1~3种未知杂质,杂质A是最大已知杂质,结果中位数为0.22%~0.31%,最大未知杂质为长春西汀结构类似物,结果中位数为0.034%~0.082%,杂质总量结果中位数为0.53%~0.73%。不同厂家的杂质谱不尽相同。结论本法适用于长春西汀注射液中有关物质的测定和质量控制,工艺处方分析结果表明,糠醛和苯甲醛为辅料维生素C和苯甲醇氧化降解引入的杂质,杂质A、B、C、D、F和长春胺为工艺杂质,其中杂质A、F也是降解杂质。
Objective To determine the related substances and impurity profile in vinpocetine injection,and to identify the relationship between the sources of impurities and the production.Methods The separation was performed on an ACE Excel C_(18)(4.6 mm×250 mm,5μm)column-1 with gradient elution with the mobile phase consisting of acetonitrile-0.2 mol·L ammonium-acetate solution.The flow rate was 1.0 mL·min 1,the detection wavelength was 280 nm,and the column temperature was 35℃.The related substances in 79 batches of vinpocetine injection from 7 enterprises were determined.The structure of the biggest unknown impurity was estimated by UHPLC-Q-TOF,and the impurities were identified and attributed to the source of the impurities by combining the damage test,process analysis and simulated sterilization process.Results The optimized detection method effectively separated and determined 8 known impurities in vinpocetine,including impurity A,B,C,D,F,vincamine,benzaldehyde and furfural.Finally 3~6 known impurities and 1~3 unknown impurities were detected in the 7 enterprises.Impurity A was the biggest known impurity,and the median result of each manufacturer was 0.22%~0.31%.The biggest unknown impurity showed similar structure with vinpocetine with the median of each manufacturer at 0.034%~0.082%;and the median of total impurity at 0.53%~0.73%.The impurity spectrum varied with manufacturers.Conclusion The proposed chromatographic method can be used for the analysis of related substances and quality control of the injection.Furfural and benzaldehyde are impurities introduced by the degradation of excipients.ImpurityA,B,C,D,F and vincamine are impurities from the process,and impurities A and F are also degradation impurities.
作者
王发
杜玮
舒思雨
李继
刘雪峰
WANG Fa;DU Wei;SHU Si-yu;LI Ji;LIU Xue-feng(Shaanxi Institute for Food and Drug Control,Xi’an 710065)
出处
《中南药学》
CAS
2024年第9期2446-2450,共5页
Central South Pharmacy
基金
陕西省重点研发计划(No.2021SF-304)。
关键词
HPLC
长春西汀
有关物质
辅料
杂质谱
工艺杂质
降解杂质
HPLC
vinpocetine
related substance
auxiliary material
impurity profile
process impurity
degradation impurity
