LC-MS法鉴定艾滋病治疗药物去羟肌苷的有关物质  

LC-MS identification of the degradation products of didanosine

作　　者：杜明荦[1] 连莹[1] 张军霞[1] 陈炜[1] 仲平[1] 

机构地区：[1]河南省食品药品检验所,郑州450003

出　　处：《药物分析杂志》2017年第11期1986-1993,共8页Chinese Journal of Pharmaceutical Analysis

基　　金：全球基金资助项目(No.GF2012-14)

摘　　要：目的:采用高效液相色谱-质谱联用技术鉴定艾滋病治疗药物去羟肌苷的有关物质结构。方法:Inert Surstain C_(18)(250 mm×4.6 mm,5μm)色谱柱,以0.386%醋酸铵溶液加氨水调节p H至8.0为流动相A,以甲醇-乙腈(50∶50)为流动相B,进行梯度洗脱,电喷雾正离子化高分辨TOF/MS和MS/MS检测并解析有关物质结构。TOF/MS雾化气压力345 k Pa,温度350℃,干燥气流量10 L·min^(-1),毛细管电压4 k V,碎片电压100 V,MS/MS测定氩气CID压力0.2 Pa,碰撞能量25 e V。结果:检测到去羟肌苷原料中共有8个有关物质,通过有机反应机制分析和质谱解析鉴定了他们的结构,他们分别是9-(2-氧基-丁酸)-1,4,5,7,8,9-六氢-嘌呤-6-酮、次黄嘌呤、肌苷、2′-去氧肌苷、9-(2-羟基-乙酰基)-1,9-双氢-嘌呤-6-酮、3′-去氧肌苷、2′,3′-脱水肌苷、9-(2-羟乙基-4-丙酸甲酯-四氢呋喃)-1,9-双氢-6H-嘌呤-6-酮。结论:采用色谱-质谱联用技术能有效地鉴定去羟肌苷的有关物质,可为其质量控制研究提供参考。Objective： To identify the related substances of didanosine by hyphenated LC-MS methods. Methods： The separation was carried out on InertSurstain C18 （ 250 mm× 4.6 mm, 5 mm ） column with mobile phase consisting of 0.386% ammonium acetate solution （ adjust pH=8.0 by amonia water solution ） and metbanol-acetonitrile （ 50 ： 50 ） by gradient elution. The related substances were detected by positive ESI high resolution TOF/MS and their MS/MS spectra were determined as well. The conditions of TOF/MS were as follows ： nebulizer pressure 345 kPa, gas temperature 350 ℃, drying gas flow 10 L·min-1, capillary voltage 4 kV and fragmentorlO0 V. The argon collision gas pressure of MS/MS was set at 0.2 Pa, and the collision energy at 25 eV. Results： There were 8 related substances in didanosine and their chemical structures were determined through the elucidation of their accurate TOF/MS data, the corresponding product MS spectra and further validated with the organic reaction mechanisms. The impurities were identified as 9- （ 2-oxo-4-butiric acid ） -1,4, 5, 7, 8,9- hexahydro-purin-6-amine, hypoxanthine, inosine, 2′-deoxyinosine, 9- （ 2-hydroxy-acetyl ） -1,9-dihydrogen-purin-6-amine, 3′ -deoxyinosine, 2′, 3′-anhydroinosine, 9-（ 2-ethoxy-4-methyl propionate-tetrahydrofuran ）- 1,9-dihydrogen-6H-pufin-6-amine. Conclusion： The LC-MS method is useful for the identification of related substances in pharmaceuticals. The related substances found in didanosine are valuable for its quality control.

关 键 词：艾滋病治疗药物 嘌呤核苷类药物 去羟肌苷 杂质鉴定 9-(2-氧基-丁酸)-1 4 5 7 8 9-六 

分 类 号：R917[医药卫生—药物分析学]