Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples  

作　　者：Alongkorn Kurilung Suphitcha Limjiasahapong Khwanta Kaewnarin Pattipong Wisanpitayakorn Narumol Jariyasopit Kwanjeera Wanichthanarak Sitanan Sartyoungkul Stephen Choong Chee Wong Nuankanya Sathirapongsasuti Chagriya Kitiyakara Yongyut Sirivatanauksorn Sakda Khoomrung 

机构地区：[1]Siriraj Center of Research Excellent in Metabolomics and Systems Biology(SiCORE-MSB),Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,10700,Thailand [2]Siriraj Metabolomics and Phenomics Center,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,10700,Thailand [3]Department of Biomedical Informatics,University of Arkansas for Medical Sciences,Little Rock,AR,72205,USA [4]SingHealth Duke-NUS Institute of Biodiversity Medicine,National Cancer Centre Singapore,168583,Singapore [5]Waters Pacific Pte.,Ltd.,Singapore,117528,Singapore [6]Program in Translational Medicine,Faculty of Medicine Ramathibodi Hospital,Mahidol University,Bangkok,10400,Thailand [7]Chakri Naruebodindra Medical Institute,Faculty of Medicine Ramathibodi Hospital,Mahidol University,Samut Prakan,10540,Thailand [8]Department of Medicine,Ramathibodi Hospital,Mahidol University,Bangkok,10400,Thailand [9]Department of Biochemistry,Faculty of Medicine Siriraj Hospital,Mahidol University,Bangkok,10700,Thailand [10]Center of Excellence for Innovation in Chemistry(PERCH-CIC),Faculty of Science,Mahidol University,Bangkok,10400,Thailand

出　　处：《Journal of Pharmaceutical Analysis》2024年第5期733-743,共11页药物分析学报（英文版）

基　　金：supported by the Postdoctoral Fellowship Program(Grant No.:(IO)R016320001)by Mahidol University,Thailand.;supported by Mahidol University,Thailand(to Associate Professor Sakda Khoomrung);funding support from the National Science,Research and Innovation Fund(NSRF)via the Program Management Unit for Human Resources&Institutional Development,Research and Innovation,Thailand(Grant No.:B36G660007).

摘　　要：The collision cross-sections(CCS)measurement using ion mobility spectrometry(IMS)in combination with mass spectrometry(MS)offers a great opportunity to increase confidence in metabolite identification.However,owing to the lack of sensitivity and resolution,IMS has an analytical challenge in studying the CCS values of very low-molecular-weight metabolites(VLMs250 Da).Here,we describe an analytical method using ultrahigh-performance liquid chromatography(UPLC)coupled to a traveling wave ion mobility-quadrupole-time-of-flight mass spectrometer optimized for the measurement of VLMs in human urine samples.The experimental CCS values,along with mass spectral properties,were reported for the 174 metabolites.The experimental data included the mass-to-charge ratio(m/z),retention time(RT),tandem MS(MS/MS)spectra,and CCS values.Among the studied metabolites,263 traveling wave ion mobility spectrometry(TWIMS)-derived CCS values(TWCCSN2)were reported for the first time,and more than 70%of these were CCS values of VLMs.The TWCCSN2 values were highly repeatable,with inter-day variations of<1%relative standard deviation(RSD).The developed method revealed excellent TWCCSN2 accuracy with a CCS difference(DCCS)within±2%of the reported drift tube IMS(DTIMS)and TWIMS CCS values.The complexity of the urine matrix did not affect the precision of the method,as evidenced by DCCS within±1.92%.According to the Metabolomics Standards Initiative,55 urinary metabolites were identified with a confidence level of 1.Among these 55 metabolites,53(96%)were VLMs.The larger number of confirmed compounds found in this study was a result of the addition of TWCCSN2 values,which clearly increased metabolite identification confidence.

关 键 词：Very low-molecular-weight metabolites Traveling wave ion mobility Collision cross-section Human urine 

分 类 号：R563.1[医药卫生—呼吸系统]