LC-MS法测定肌苷片和肌苷口服溶液中的杂质  

Determinnation of impurities in Inosine tablets and Inosine oral solution by LC-MS

作　　者：周明 胡亮 黄婧 李琦 ZHOU Ming;HU Liang;HUANG Jing;LI Qi(Hunan Engineering&Technology Research Center for Pharmaceutical Quality Evaluation,Hunan Center for Pharmaceutical Excipients Control,Hunan Institute for Drug Control,Changsha,Hunan,410001 P.R.China;Xiamen Institute for Food and Drug Quality Control,Xiamen,Fujian,361000 P.R.China)

机构地区：[1]湖南省药品检验研究院湖南药用辅料检验检测中心,湖南省药品质量评价工程技术研究中心,湖南长沙410001 [2]厦门市食品药品质量检验研究院,福建厦门361000

出　　处：《华西药学杂志》2021年第5期574-578,共5页West China Journal of Pharmaceutical Sciences

摘　　要：目的研究肌苷片和肌苷口服溶液中的杂质。方法采用HPLC法测定肌苷片和肌苷口服溶液中的有关物质;采用ADMET Predictor软件预测和评价相关杂质的遗传毒性。结果建立了肌苷的杂质谱,进行了杂质溯源,全面预测了肌苷、鸟苷、腺苷与次黄嘌呤的毒理性质。结论通过LC-MS分析,明确了15个杂质中的鸟苷、腺苷与次黄嘌呤3个杂质;肌苷、鸟苷和腺苷表现出大鼠的致癌性和一定的致突变性,次黄嘌呤表现出肝毒性,但4种杂质的整体毒性风险不大。OBJECTIVE To study on the impurities in Inosine tablets(IT)and Inosine oral solution(IOS).METHODS The related substances of IT and IOS were determined by HPLC,and the genetic toxicity of related impurities were predicted and evaluated by ADMET Predictor.RESULTS The impurity spectrum of inosine was established and traced.The genetic toxicity of inosine,guanosine,adenosine and hypoxanthine were comprehensively predicted.CONCLUSION Three impurities(guanosine,adenosine,and hypoxanthine)among 15 impurities were identified by LC-MS analysis.Inosine,guanosine,and adenosine show carcinogenicity and mutagenicity in rats,and hypoxanthine show hepatotoxicity,but the overall toxicity risk of these four drugs is not high.

关 键 词：肌苷 次黄嘌呤 鸟苷 腺苷 高效液相色谱法 液质联用法 有关物质 杂质 毒性 

分 类 号：R917[医药卫生—药物分析学]