Determination of Effective Constituents in Imported Novel Coronavirus Specific Drugs by High Performance Liquid Chromatography Tandem Mass Spectrometry
摘 要
为确保进口新冠药物质量,提出了题示方法。样品(约0.600 g)用50%(体积分数,下同)甲醇溶液15 mL超声溶解20 min,并定容至25 mL。取上述溶液10 mL离心,取上清液100 μL用50%甲醇溶液定容至100 mL。所得溶液采用ZORBAX Eclipse XDB-C18柱分离,以不同体积比的甲醇-0.1%(体积分数)三氯乙酸溶液混合液为流动相进行梯度洗脱,多反应监测(MRM)模式进行质谱分析。结果表明,奈玛特韦和利托那韦的质量浓度在2~200 μg·L-1内与对应的峰面积呈线性关系,测定下限(10S/N)分别为0.85,0.63 μg·L-1。按照标准加入法进行回收试验,回收率为92.5%~115%,测定值的相对标准偏差(n=6)小于8.0%。方法用于30批实际样品的分析,仅9个样品中检出奈玛特韦和利托那韦有效成分。
Abstract
In order to ensure the quality of imported novel coronavirus specific drugs, the method mentioned by the title was proposed. The sample (about 0.600 g) was dissolved in 15 mL of 50% (volume fraction, the same below) methanol solution by ultrasound for 20 min, and made its volume up to 25 mL. 10 mL of the above solution was centrifuged, then 100 μL of the supernatant was taken, and made its volume up to 100 mL with 50% methanol solution. The obtained solution was separated on ZORBAX Eclipse XDB-C18 column, using a mixture of methanol and 0.1%(volume fraction) trichloroacetic acid solution at different volume ratios as mobile phase for gradient elution. As shown by the results, linear relationships between values of the corresponding peak area and mass concentration of nirmatrelvir and ritonavir were found in the range of 2-200 μg·L-1, with lower limits of determination (10S/N) of 0.85 μg·L-1 and 0.63 μg·L-1, respectively. Test for recovery was made by the standard addition method, giving the results in the range of 92.5%-115%, with RSDs (n=6) of the determined values less than 8.0%. This method was used for the analysis of 30 batches of actual samples, and the effective constituents of nirmatrelvir and ritonavir were detected in only 9 samples.
中图分类号 O657.63 DOI 10.11973/lhjy-hx202312005
所属栏目 工作简报
基金项目 国家重点研发计划项目(2022YFF0607200)
收稿日期 2023/4/11
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备注麦晓霞,高级工程师,硕士研究生,研究方向为有机质谱分析
引用该论文: MAI Xiaoxia,TAN Zhiyi,ZHANG Haifeng,ZHANG Zihao,XU Jinmei,YAN Zhuowen,XIAO Qian,LIU Yingfeng,ZHENG Jianguo. Determination of Effective Constituents in Imported Novel Coronavirus Specific Drugs by High Performance Liquid Chromatography Tandem Mass Spectrometry[J]. Physical Testing and Chemical Analysis part B:Chemical Analysis, 2023, 59(12): 1395~1400
麦晓霞,谭智毅,张海峰,张子豪,徐金梅,颜焯文,肖前,刘莹峰,郑建国. 高效液相色谱-串联质谱法测定进口新冠特效药中有效成分的含量[J]. 理化检验-化学分册, 2023, 59(12): 1395~1400
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参考文献
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【2】潘敏,张田婧,常双,等.老年人新型冠状病毒感染小分子抗病毒药物治疗建议[J].中国药理学通报, 2023,39(3):425-430.
【3】时美慧,李俭,甘慧,等.快速测定人血浆中洛匹那韦/利托那韦浓度的LC-MS/MS方法建立[J].国际药学研究杂志, 2016,43(1):162-166.
【4】HUANG X J, XU Y L, YANG Q Y, et al. Efficacy and biological safety of lopinavir/ritonavir based anti-retroviral therapy in HIV-1-infected patients:A meta-analysis of randomized controlled trials[J]. Scientific Reports, 2015,5:8528.
【5】吕佳乐,刘正才,姚闽娜,等.超高效液相色谱-串联质谱法测定鸡肉中4种蛋白酶抑制剂[J].色谱, 2020,38(2):212-217.
【6】CHU L X, WU Y, DUAN C L, et al. Simultaneous quantitation of zidovudine, efavirenz, lopinavir and ritonavir in human hair by liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry[J]. Journal of Chromatography B, 2018,1097/1098:54-63.
【7】YADAV M, RAO R, KURANI H, et al. Application of a rapid and selective method for the simultaneous determination of protease inhibitors, lopinavir and ritonavir in human plasma by UPLC-ESI-MS/MS for bioequivalence study in Indian subjects[J]. Journal of Pharmaceutical and Biomedical Analysis, 2009,49(4):1115-1122.
【8】DAS MISHRA T, KURANI H, SINGHAL P, et al. Simultaneous quantitation of HIV-protease inhibitors ritonavir, lopinavir and indinavir in human plasma by UPLC-ESI-MS-MS[J]. Journal of Chromatographic Science, 2012,50(7):625-635.
【9】谢静,唐铭擎,丁立生,等.抗COVID-19药物的临床分析研究进展[J].中国现代应用药学, 2020,37(6):646-652.
【10】MARZINKE M A, BREAUD A, PARSONS T L, et al. The development and validation of a method using high-resolution mass spectrometry (HRMS) for the qualitative detection of antiretroviral agents in human blood[J]. Clinica Chimica Acta, 2014,433:157-168.
【11】熊歆,应颖秋,张现化,等.液相色谱-质谱联用同时测定人血浆中奈玛特韦、利托那韦及巴瑞替尼的浓度[J/OL]. (2023-04-11). https://kns.cnki.net/kcms/detail/11.2162.R.20230302.1842.008.html.
【12】寇惠娟,叶敏,付强,等.高效液相色谱法同时测定人血浆中洛匹那韦和利托那韦浓度[J].中国科学:生命科学, 2012,42(4):326-332.
【13】胡玉荣,刘晓艳,阿有梅,等.反相高效液相色谱法测定利托那韦血浆药物浓度[J].药物分析杂志, 2006,26(10):1434-1436.
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