不同来源复方甘草酸铵注射液中氨基酸稳定性差异及降解成因研究  

Study on the stability differences and degradation causes of amino acid in compound ammonium glycyrrhizinate injection from different sources

作　　者：谢升谷 黄艳[2] 何佳佳 孙逍 倪维芳 陶巧凤 XIE Sheng-gu;HUANG Yan;HE Jia-jia;SUN Xiao;NI Wei-fang;TAO Qiao-feng(Zhejiang Institute for Food and Drug Control,National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou 310052,China;Zhejiang University of Technology,Hangzhou 310014,China)

机构地区：[1]浙江省食品药品检验研究院、国家药品监督管理局仿制药评价关键技术重点实验室浙江省药品接触材料质量控制研究重点实验室,杭州310052 [2]浙江工业大学,杭州310014

出　　处：《药物分析杂志》2023年第2期297-304,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：浙江省药品监督管理局科技计划项目(2021005);浙江省药品监督管理与产业发展研究会课题(ZYH2021003)。

摘　　要：目的:建立HPLC法测定复方甘草酸铵注射液中甘氨酸与盐酸半胱氨酸的含量,运用离子色谱法测定抗氧剂亚硫酸根离子及氧化产物硫酸根离子的含量,并对不同来源样品的氨基酸稳定性差异及降解成因进行研究、分析。方法:HPLC法采用Agilent Eclipse XDB-C_(18)色谱柱(150 mm×4.6 mm,5μm),流动相为甲醇-0.01 mol·L^(-1)磷酸盐缓冲液(磷酸调pH至2.15±0.02)(5∶95),检测波长为210 nm。离子色谱法采用IonPac AS11-HC柱(250 mm×4 mm),淋洗液为15 mmol·L^(-1)氢氧化钾溶液,检测器为电导检测器。结果:不同生产企业的复方甘草酸铵注射液中,甘氨酸含量均符合标准规定;盐酸半胱氨酸含量为标示量的76.4%~94.3%,亚硫酸钠为处方量的75.7%~96.1%。结论:本法无需样品前处理且准确度高,可为复方甘草酸铵注射液的质量控制提供参考。不同来源的注射液中甘氨酸稳定性较好;盐酸半胱氨酸含量参差不齐,部分样品含量较低、稳定性较差。运用离子色谱法测定亚硫酸钠含量稳定性好,准确度较高。不同来源的样品中亚硫酸钠含量存在差异,且在长期贮存过程中亚硫酸钠无法很好地防止盐酸半胱氨酸发生氧化降解,且各企业样品的降解程度也有所不同。生产企业需进一步优化制剂的处方及生产工艺以控制不稳定成分的降解,从而提高药品质量。Objective:The HPLC method was established to determine the contents of glycine and cysteine-HCl in compound ammonium glycyrrhizinate injection,and ion chromatography was used to determine the contents of sulfite ion and its oxidation product sulfate ion,and the differences of amino acid stability and its causes of samples from different sources were studied and analyzed.Methods:Agilent Eclipse XDB-C_(18)column(150 mm×4.6 mm,5μm)was used.The mobile phase was methanol-0.01 mol·L^(-1)phosphate buffer(adjusted to pH 2.15±0.02 with phosphoric acid)(5∶95).The detection wavelength was 210 nm.IonPac AS11-HC column(250 mm×4 mm)was used for ion chromatography,the eluent was 15 mmol·L^(-1)potassium hydroxide solution,and the detector was a conductivity detector.Results:The content of glycine in compound ammonium glycyrrhizinate injection from different manufacturers met the standard requirements.The contents of cysteine-HCl were 76.4%-94.3%,and that of sodium sulfite were 75.7%-96.1%.Conclusion:The new HPLC method needs no sample pretreatment and is accurate,which provids reference for the quality control of compound ammonium glycyrrhizinate Injection.Glycines in injection from different sources are stable.The contents of cysteine-HCl are uneven,and the contents in some samples are low and the stability is poor.The determination method of sodium sulfite by ion chromatography shows good stability and high accuracy.The contents of sodium sulfite in samples from different sources are different,and the oxidation of sodium sulfite and cysteine-HCl are synchronous during long-term storage,and the degradation degrees of samples from various enterprises are also different.Manufacturers need to further optimize the formulation and production process of preparations to control the degradation of unstable ingredients,thereby improving the quality of medicines.

关 键 词：复方甘草酸铵注射液 甘氨酸 盐酸半胱氨酸 亚硫酸钠 稳定性 处方工艺 

分 类 号：R917[医药卫生—药物分析学]