六味地黄丸中山药掺伪投料的鉴定方法建立和安全性风险评价  

Establishing identification methods and assessing safety risk of adulterated ingredients of yam in Liuwei Dihuang Pill

作　　者：权琦琦 王亚琼 钱叶飞 张超 陈卫 姚卫峰[1] QUAN Qi-qi;WANG Ya-qiong;QIAN Ye-fei;ZHANG Chao;CHEN Wei;YAO Wei-feng(Nanjing University of Chinese Medicine,Nanjing 210023,China;Suzhou Pharmaceutical Inspection and Testing Research Center,Suzhou 215000,China)

机构地区：[1]南京中医药大学,江苏南京210023 [2]苏州市药品检验检测研究中心,江苏苏州215000

出　　处：《时珍国医国药》2025年第1期67-74,共8页Lishizhen Medicine and Materia Medica Research

基　　金：江苏省药学会—奥赛康医院药学科研基金项目(A202318);江苏省药品监督管理局药品监管科学科研计划课题(202128)。

摘　　要：目的建立UPLC-MS/MS测定六味地黄丸中山药掺伪的特征成分伪原薯蓣皂苷以及离子色谱法测定六味地黄丸中山药掺伪后产生的氰化物含量的方法,综合考察山药掺伪投料的安全性风险。方法利用液相色谱-质谱联用仪采用正离子多反应监测(MRM)监测模式建立方法,以伪原薯蓣皂苷为目标成分,筛查六味地黄丸不同制剂中山药投料掺伪的情况,并利用离子色谱仪,采用安培检测器和银工作电极,测定六味地黄丸不同制剂中氰化物的残留状况。结果所建立UP⁃LC-MS/MS方法中伪原薯蓣皂苷在5.083~508.32 ng·mL^(-1)之间呈良好的线性关系,样品加标回收率为97.24%~97.49%,方法稳定,对六味地黄丸制剂(263批)进行筛查检验,结果检出4批阳性;随后对所建立离子色谱法进行考察,氰根离子在1.22~5000.0 ng·mL^(-1)的浓度范围内呈良好的线性关系,检测限为0.92 ng·mL^(-1),定量限为1.16 ng·mL^(-1)。对于已检出山药掺伪阳性的样品进行氰化物风险评价,结果表明六味地黄丸中氰化物的含量低于检出限,无安全性风险。结论实验所建立的山药掺伪的特征成分伪原薯蓣皂苷以及产生的氰化物含量测试结果准确、可靠,一方面可以有效筛查山药掺伪情况,另一方面又可以进一步评价制剂的服用安全性,为随后的质量标准提高和整体监管质量评估提供了较为合理的技术手段。Objective To establish an UPLC-MS/MS method to determine diosgenin and the characteristic component of yam adulteration in Liuwei Dihuang Pill(LDP),and an ion chromatography method to determine cyanide content after yam adulteration in LDP,and comprehensively investigate the safety risk of yam adulterated ingredients.Methods The positive ion multiple reaction monitoring(MRM)mode was established by liquid chromatography-mass spectrometry(LC-MS/MS),and the spurious dioscin was used as the target component to screen the adulteration of yam in different preparations of LDP.The cyanide residue in different preparations of LDP was determined by ion chromatograph with amperometric detector and silver working electrode.Results The established UPLC-MS/MS method was stable,showing a good linear relationship between the concentration of pseudo-dioscin and the range of 5.083 ng·mL^(-1)and 508.32 ng·mL^(-1),and the recovery rate of sample spiked was 97.24%to 97.49%.A total of 263 batches of LDP were screened,among which 4 were positive.The established ion chromatography method showed a good linear relationship in the concentration range of 1.22-5000.0 ng·mL^(-1).The detection limit was 0.92 ng·mL^(-1),and the limit of quantification was 1.16 ng·mL^(-1).The cyanide risk assessment carried out on the samples with yam adulteration was positive,showing that the cyanide content in LDP was lower than the detection limit,and there was no safety risk.Conclusion The test results of dioscin,the characteristic component of yam adulteration,and the cyanide content are accurate and reliable,which can effectively screen the adulteration of yam on the one hand,and further evaluate the safety of the preparation on the other,thus providing a more reasonable technical means for the subsequent improvement of quality standards and the overall supervision quality assessment.

关 键 词：超高效液相色谱串联三重四级杆质谱法 离子色谱 六味地黄丸 氰化物 木薯 伪原薯蓣皂苷 

分 类 号：R284.1[医药卫生—中药学]