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

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

doi:10.1016/j.jpha.2023.12.011

Volume 14 Issue 5

May 2024

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Article Navigation > Journal of Pharmaceutical Analysis > 2024 > 14(5): 100921

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. Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100921. doi: 10.1016/j.jpha.2023.12.011

Citation:

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. Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100921. doi: 10.1016/j.jpha.2023.12.011

Citation:

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. Measurement of very low-molecular weight metabolites by traveling wave ion mobility and its use in human urine samples[J]. Journal of Pharmaceutical Analysis, 2024, 14(5): 100921. doi: 10.1016/j.jpha.2023.12.011

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

doi: 10.1016/j.jpha.2023.12.011

a. Siriraj Center of Research Excellent in Metabolomics and Systems Biology (SiCORE-MSB), Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand;
b. Siriraj Metabolomics and Phenomics Center, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand;
c. Department of Biomedical Informatics, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA;
d. SingHealth Duke-NUS Institute of Biodiversity Medicine, National Cancer Centre Singapore, 168583, Singapore;
e. Waters Pacific Pte., Ltd., Singapore, 117528, Singapore;
f. Program in Translational Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand;
g. Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan, 10540, Thailand;
h. Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand;
i. Department of Biochemistry, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, 10700, Thailand;
j. Center of Excellence for Innovation in Chemistry (PERCH-CIC), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

Funds:

Dr. Alongkorn Kurilung was supported by the Postdoctoral Fellowship Program (Grant No.: (IO) R016320001) by Mahidol University, Thailand. This research project was supported by Mahidol University, Thailand (to Associate Professor Sakda Khoomrung). This research has received 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). The Center of Excellence for Innovation in Chemistry (PERCH-CIC), Ministry of Higher Education, Science, Research, and Innovation, Thailand, are gratefully acknowledged. This project is partially supported by the Research Excellence Development (RED) program, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand.

Received Date: Jun. 21, 2023
Accepted Date: Dec. 13, 2023
Rev Recd Date: Nov. 17, 2023
Publish Date: May 30, 2024

Abstract

Abstract

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 (VLMs ≤ 250 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 (^TWCCS_N2) were reported for the first time, and more than 70% of these were CCS values of VLMs. The ^TWCCS_N2 values were highly repeatable, with inter-day variations of <1% relative standard deviation (RSD). The developed method revealed excellent ^TWCCS_N2 accuracy with a CCS difference (△CCS) 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 △CCS 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 ^TWCCS_N2 values, which clearly increased metabolite identification confidence.
- Very low-molecular-weight metabolites,
- Traveling wave ion mobility,
- Collision cross-section,
- Human urine

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References(59)

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