目的 建立硫酸核糖霉素杂质谱的在线膜脱盐液相色谱-静电轨道阱质谱(LC-Orbitrap HRMS)研究方法,消除流动相中三氟乙酸等对电喷雾离子化的抑制作用。方法 采用Thermo Aminoglycoside (RP18 4.6 mm×150 mm,3 μm)色谱柱,以体积分数0.20%五氟丙酸0.15%三氟乙酸溶液-乙腈(99∶1)为流动相1 mL·min-1等度洗脱,柱后分流(3∶2)电喷雾正离子化质谱检测。采用在线膜脱盐消除流动相中五氟丙酸和三氟乙酸对电喷雾离子化的抑制作用。结果 测得硫酸核糖霉素中11个有关物质,经质谱解析推测了其结构,分析确定其来源主要为合成中间体、副产物或降解杂质。结论 研究结果可为硫酸核糖霉素质量控制提供参考。
Abstract
OBJECTIVE To establish a liquid chromatography electrostatic orbittrap mass spectrometry (LC-Orbitrap HRMS) method for impurity profile of ribostamycin sulfate with online membrane desalting to eliminate the inhibition of trifluoroacetic acid in mobile phase on electrospray ionization. METHODS The separation was carried out on a thermo Aminoglycoside (RP18 4.6 mm×150 mm, 3 μm) column, using 0.20% pentafluoropropionic acid 0.15% trifluoroacetic acid solution and acetonitrile mixture (99∶1) as mobile phase with isocratic elution at a flow rate of 1 mL·min-1, post column effluent in split flow (3∶2) was delivered for electrospray positive ionization electrostatic orbit trap mass spectrometry detection. The inhibition of pentafluoropropionic acid and trifluoroacetic acid on electrospray ionization in mobile phase was eliminated by online anion exchange membrane desalination. RESULTS Eleven related substances in ribostamycin sulfate were determined, and their structures were elucidated by mass spectrometry analysis. Their sources were determined mainly to be synthetic intermediates, by-products, or degradation impurities. CONCLUSION These results can provide references for the quality control of ribostamycin sulfate.
关键词
硫酸核糖霉素 /
杂质谱 /
液相色谱-静电场轨道阱质谱法
{{custom_keyword}} /
Key words
ribostamycin sulfate /
impurity profile /
liquid chromatography-electrostatic field orbitrap mass spectrometry(LC-Orbitrap HRMS)
{{custom_keyword}} /
中图分类号：
R917
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] KUDO F, EGUCHI T. Aminoglycoside antibiotics: new insights into the biosynthetic machinery of old drugs[J]. Chem Rec, 2016, 1(16): 4-18.
[2] LIU Y H, DAI X M, ZHANG X J, et al. Pharmacokinetics of ribostamycin in healthy volunteers[J]. J Dalian Med Univ (大连医科大学学报), 1985, 7(1):16-20.
[3] JP 18[S]. 2018:1638-1639.
[4] KP 10[S]. 2017: 1048-1049.
[5] Ch.P (2020) Vol Ⅱ(中国药典2020年版.二部)[S]. 2020:1612-1613.
[6] LU J G, GU Y. Inspecting the stability of neamine in ribostamycin sulfate by HPLC[J]. J China Pharm (中国药房),2006,17(7):533-535.
[7] TENG Y M X, WANG F X. Biosynthesis of aminoglycoside antibiotics focusing on 2-deoxystreptomycin[J]. World Notes on Antibiot (国外医药 抗生素分册), 1982:361-362.
[8] CHEN D. Study on the quality evaluation method of netilmicin sulfate and its injection[D]. Nanjing: China Pharmaceutical University, 2017.
[9] SHI S L, HOU Y R, GENG Y, et al. High performance liquid chromatography combined with pulsed amperometric detection for the analysis of ribostamycin sulfate[J]. Chin Pharm J (中国药学杂志), 2019, 54(4):321-326.
[10] YUAN Y Z, ZHANG M, HU C Q. Advances in the components analysis of aminoglycosides[J]. Chin Pharm J (中国药学杂志), 2017, 52(20):1772-1779
[11] YUAN Y Z, ZHANG M, JING S H. Progress on qulity control of aminoglycosides antibiotics[J]. Chin J Antibiot (中国抗生素杂志), 2019, 44(11):1244-1255.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
“重大新药创制”科技重大专项课题“化药制剂质量评价关键技术研究”项目资助 (2015ZX09303001)
{{custom_fund}}
PDF(1285 KB)
