Drug adulteration analysis based on complexation with cyclodextrin and metal ions using ion mobility spectrometry  

作　　者：Zhigang Liang Huanhuan Wang Fangling Wu Longfei Wang Chenwei Li Chuan-Fan Ding 

机构地区：[1]Department of Thoracic Surgery,Ningbo First Hospital,Ningbo University,Ningbo,Zhejiang,315010,China [2]Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis of Zhejiang Province,Institute of Mass Spectrometry,School of Material Science and Chemical Engineering,Ningbo University,Ningbo,Zhejiang,315211,China

出　　处：《Journal of Pharmaceutical Analysis》2023年第3期287-295,共9页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.:22004074 and 21927805);Zhejiang Natural Science Foundation(Grant No.:LY22B050006);Foundation of Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry Technology and Molecular Detection(Grant No.:AMSMAKF2102).

摘　　要：Drug adulteration and contamination are serious threats to human health therefore,their accurate monitoring is very important.Allopurinol(Alp)and theophylline(Thp)are commonly used drugs for the treatment of gout and bronchitis,while their isomers hypoxanthine(Hyt)and theobromine(Thm)have no effect and affect the efficacy of the drug.In this work,the drug isomers of Alp/Hyt and Thp/Thm are simply mixed withα-,β-,γ-cyclodextrin(CD)and metal ions and separated using trapped ion mobility spectrometry-mass spectrometry(TIMS-MS).TIMS-MS results showed that Alp/Hyt and Thp/Thm isomers could interact with CD and metal ions and form corresponding binary or ternary complexes to achieve their TIMS separation.Different metal ions and CDs showed different separation effect for the isomers,among which Alp and Hyt could be successfully distinguished from the complexes of[Alp/Hyt+γ-CD+Cu–H]^(+)with separation resolution(RP–P)of 1.51;whereas Thp and Thm could be baseline separated by[Thp/Thm+γ-CD+Ca–H]^(+)with RP–P of 1.96.Besides,chemical calculations revealed that the complexes were in the inclusion forms,and microscopic interactions were somewhat different,making their mobility separation.Moreover,relative and absolute quantification was investigated with an internal standard to determine the precise isomers content,and good linearity(R^(2)>0.99)was obtained.Finally,the method was applied for the adulteration detection where different drugs and urine were analyzed.In addition,due to the advantages of fast speed,simple operation,high sensitivity,and no chromatographic separation required,the proposed method provides an effective strategy for the drug adulteration detection of isomers.

关 键 词：Drug isomer ADULTERATION Separation Ion mobility Chemical calculations 

分 类 号：R927.1[医药卫生—药学]