基于UHPLC-LTQ-Orbitrap MS^(n)技术的小儿感冒口服液潜在苦味关键质量属性研究  

Characterization of potential bitterness critical quality attributes in Xiaoer Ganmao Oral Liquid based on UHPLC-LTQ-Orbitrap MS^(n)

作　　者：王晓萌 陆影 胡小艳 马金辰 郭新雨 韩燕雨 王静 张晓梦[1,2] 李明爽 李楠 戴幸星 姚璐[3] 杜菁[3] 吴志生 WANG Xiao-meng;LU Ying;HU Xiao-yan;MA Jin-chen;GUO Xin-yu;HAN Yan-yu;WANG Jing;ZHANG Xiao-meng;LI Ming-shuang;LI Nan;DAI Xing-xing;YAO Lu;DU Jing;WU Zhi-sheng(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Engineering Research Center of Chinese Medicine Production and New Drug Development,Beijing 102488,China;Beijing Tongrentang Technology Development Co.,Ltd.,Beijing 100079,China)

机构地区：[1]北京中医药大学中药学院,北京102488 [2]中药制药与新药开发教育部工程研究中心,北京102488 [3]北京同仁堂科技发展股份有限公司,北京100079

出　　处：《药学学报》2023年第10期2882-2889,共8页Acta Pharmaceutica Sinica

基　　金：国家重点研发计划项目(2022YFC3501902);国家优秀青年科学基金项目(82022073);国家自然科学基金项目(82274110);中央高校基本科研业务费北京中医药大学揭榜挂帅项目(2022-JYB-JBZR-018,2022-JYB-JBZR-019)。

摘　　要：采用超高效液相色谱-线性离子阱-串联静电场轨道阱质谱(UHPLC-LTQ-Orbitrap MS^(n))联合BitterX数据库对真实生产世界小儿感冒口服液无糖中间体的潜在苦味关键质量属性进行辨识。采用Acquity UPLC BEH C_(18)色谱柱(100 mm×2.1 mm,1.7μm);流动相为0.1%甲酸-水溶液(A)-乙腈(B),梯度洗脱,分别在正、负离子模式下对小儿感冒口服液无糖中间体进行数据采集。根据高分辨质谱提供的准分子离子峰和多级质谱碎片,获取目标化合物的精确分子量和结构信息,结合保留时间,参照对照品、文献报道等相关数据对化合物进行分析,共鉴定包括黄酮类、生物碱类、苯丙素类等共57个化学成分。进一步,采用BitterX数据库预测化学成分与苦味受体结合的概率,辨识潜在苦味关键质量属性,最终预测得到其中包括地骨皮甲素、蒙花苷在内的33个潜在苦味化学成分。该研究较为全面地表征了小儿感冒口服液无糖中间体的化学物质基础,为筛选苦味化合物提供了有效的方法,为进一步改善小儿感冒口服液的苦味等不良口感提供了科学依据。To identify the bitter compounds of real-world Xiaoer Ganmao Oral Liquid sugar-free intermediates,an integrated strategy has been developed by using ultra-high performance liquid chromatography with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS^(n))method and Bitter X database prediction.The chro-matographic operating conditions were as follows,chromatographic column:Acquity UPLC BEH C_(18)(100 mm×2.1 mm,1.7μm),mobile phase:0.1%formic acid-water solution(A)-acetonitrile(B)with gradient elution.The data were collected in positive and negative ion modes,respectively.The accurate molecular mass and structural information of the target compounds were obtained based on quasi-molecular ions and fragmentation ions provided by high-resolution mass spectrometry.The compounds were identified by combining retention time,reference substances,reports,and other relevant data,and a total of 57 constituents including flavonoids,alkaloids,and phenylpropanoids were finally identified.Further,the BtterX database was used to predict binding probability of compounds to bitter receptors and identify potential bitter critical quality attributes,finally 33 potential bitter compounds,including kukoamine A and linarin,were predicted.This study comprehensively characterized the material basis of Xiaoer Ganmao Oral Liquid sugar-free intermediates,it provides an effective method for bitter compound screening and a reference for further improving the undesirable taste of Xiaoer Ganmao Oral Liquid.

关 键 词：关键质量属性 UHPLC-LTQ-Orbitrap MS^(n) 苦味物质 质谱分析 

分 类 号：R917[医药卫生—药物分析学]