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Profiling of chiral and achiral carboxylic acid metabolomics: synthesis and evaluation of triazine-type chiral derivatization reagents for carboxylic acids by LC-ESI-MS/MS and the application to saliva of healthy volunteers and diabetic patients

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Abstract

Novel triazine-type chiral derivatization reagents, i.e., (S)-1-(4,6-dimethoxy-1,3,5-triazin-2-yl)pyrrolidin-3-amine (DMT-3(S)-Apy) and (S)-4,6-dimethoxy-N-(pyrrolidin-3-yl)-1,3,5-triazin-2-amine (DMT-1(S)-Apy), were developed for the highly sensitive and selective detection of chiral carboxylic acids by UPLC-MS/MS analysis. Among the synthesized reagents, DMT-3(S)-Apy was a more efficient chiral reagent for the enantiomeric separation of chiral carboxylic acids in terms of separation efficiency by reversed-phase chromatography and detection sensitivity by ESI-MS/MS. The DMT-3(S)-Apy was used for the determination of 13 carboxylic acids in human saliva of healthy volunteers and diabetic patients. Various biological carboxylic acids including chiral carboxylic acids, and mono- and di-carboxylic acids were clearly identified in the saliva of healthy persons and diabetic patients. The concentrations of carboxylic acids detected in the saliva of diabetic patients were relatively higher than those in the healthy persons. Furthermore, the concentration of d-lactic acid (LA) and the ratio of d/l-LA in the diabetic patients were significantly higher than those in the healthy persons. The low ratio of d/l-LA in healthy persons was also identified to be independent of age and sex. These results suggest that the determination of the d/l-LA ratio in saliva might be applicable for the diagnosis of diabetes. Based on these observations, DMT-3(S)-Apy seems to be a useful chiral derivatization reagent for the determination not only of chiral carboxylic acids but also achiral ones. In conclusion, the proposed method using DMT-3(S)-Apy is useful for the carboxylic acid metabolomics study of various specimens.

DL-Lactic acids in saliva

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Acknowledgments

This work was supported in part by Scientific Research (C) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Takahiro Takayama, Tomohiro Kuwabara, Koichi Inoue, Kenichiro Todoroki, Jun Zhe Min & Toshimasa Toyo’oka

  2. Laboratory of Clinical Pharmaceutics and Pharmacy Practice, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan

    Toshio Maeda

  3. Department of Pharmaceutical, Numazu City Hospital, Harunoki Higashi-Shiizi, Numazu, 410-0302, Japan

    Ichiro Noge

  4. Department of Clinical and Molecular Endocrinology, Numazu City Hospital, Harunoki Higashi-Shiizi, Numazu, 401-0302, Japan

    Yutaka Kitagawa

Authors
  1. Takahiro Takayama
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  2. Tomohiro Kuwabara
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  3. Toshio Maeda
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  4. Ichiro Noge
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  5. Yutaka Kitagawa
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  6. Koichi Inoue
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  7. Kenichiro Todoroki
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  8. Jun Zhe Min
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  9. Toshimasa Toyo’oka
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Correspondence to Toshimasa Toyo’oka.

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Published in the topical collection celebrating ABCs 13th Anniversary.

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Takayama, T., Kuwabara, T., Maeda, T. et al. Profiling of chiral and achiral carboxylic acid metabolomics: synthesis and evaluation of triazine-type chiral derivatization reagents for carboxylic acids by LC-ESI-MS/MS and the application to saliva of healthy volunteers and diabetic patients. Anal Bioanal Chem 407, 1003–1014 (2015). https://doi.org/10.1007/s00216-014-8275-9

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  • DOI: https://doi.org/10.1007/s00216-014-8275-9

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