Abstract
Liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) enables the accurate and precise quantification of various analytes at very low concentrations, but it has room for improvement in analysis throughput. Multiplexing of samples in the same injection could be a promising procedure for enhancing the analysis throughput. This could be achieved by derivatization of the multiple samples with multiple isotopologous reagents. In this study, a sample-multiplexed LC/ESI-MS/MS assay using the 1-[(4-dimethylaminophenyl)carbonyl]piperazine (DAPPZ) isotopologues (2H0-, 2H3-, and 2H6-forms) was developed and validated for the simultaneous determination of primary bile acids in three different plasma samples in a single run. The developed method had satisfactory intra- and inter-assay precisions (≤ 2.3 and ≤ 4.2%, respectively) and accuracy (99.0–100.3%), and could reduce the total LC/ESI-MS/MS run time by more than 60% for 42 samples compared to the conventional method. Thus, the derivatization with the DAPPZ isotopologues worked well for enhancing the throughput of the LC/ESI-MS/MS assay of the bile acids.
Similar content being viewed by others
References
B. Shushan, Mass Spectrom. Rev., 2010, 29, 930.
K. S. Leung and B. M. Fong, Anal. Bioanal. Chem., 2014, 406, 2289.
M. Alsaleh, T. A. Barbera, R. H. Andrews, P. Sithithaworn, N. Khuntikeo, W. Loilome, P. Yongvanit, I. J. Cox, R. R. A. Syms, E. Holmes, and S. D. Taylor-Robinson, J. Clin. Exp. Hepatol., 2019, 9, 597.
B. C. Netzel, K. W. Cradic, E. T. Bro, A. B. Girtman, R. C. Cyr, R. J. Singh, and S. K. Grebe, Clin. Chem., 2011, 57, 431.
S. Ogawa, H. Kittaka, A. Nakata, K. Komatsu, T. Sugiura, M. Satoh, F. Nomura, and T. Higashi, J. Pharm. Biomed. Anal., 2017, 136, 126.
T. Higashi, M. Akaishi, M. Yokota, T. Suzuki, S. Ogawa, Y. Sugiura, T. Nishikawa, K. Nishimoto, and M. Suematsu, J. Chromatogr., B, 2018, 1092, 106.
P. J. Crick, T. W. Bentley, J. Abdel-Khalik, I. Matthews, P. T. Clayton, A. A. Morris, B. W. Bigger, C. Zerbinati, L. Tritapepe, L. Iuliano, Y. Wang, and W. J. Griffiths, Clin. Chem., 2015, 61, 400.
S. Ogawa, K. Tomaru, N. Matsumoto, S. Watanabe, and T. Higashi, Biomed. Chromatogr, 2016, 30, 29.
T. Higashi, S. Watanabe, K. Tomaru, W. Yamazaki, K. Yoshizawa, S. Ogawa, H. Nagao, K. Minato, M. Maekawa, and N. Mano, Steroids, 2017, 125, 107.
T. Matsumoto, W. Yamazaki, A. Jo, S. Ogawa, K. Mitamura, S. Ikegawa, and T. Higashi, Anal. Sci., 2018, 34, 1003.
Y. Liu, Z. Rong, D. Xiang, C. Zhang, and D. Liu, Lipids Health Dis., 2018, 17, 121.
M. Dutta, J. Cai, W. Gui, and A. D. Patterson, Anal. Bioanal. Chem., 2019, 411, 4541.
M. Turowski, N. Yamakawa, J. Meller, K. Kimata, T. Ikegami, K. Hosoya, N. Tanaka, and E. R. Thornton, J. Am. Chem. Soc., 2003, 125, 13836.
R. Thakare, Y. S. Chhonker, N. Gautam, J. A. Alamoudi, and Y. Alnouti, J. Pharm. Biomed. Anal., 2016, 128, 426.
M. Scherer, C. Gnewuch, G. Schmitz, and G. Liebisch, J. Chromatogr, B, 2009, 877, 3920.
Acknowledgments
This study was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Numbers 17K08250 and 20K06990.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Rights and permissions
About this article
Cite this article
Jo, A., Koyagi, S., Hobo, W. et al. Enhancing LC/ESI-MS/MS Throughput for Plasma Bile Acid Assay by Derivatization-based Sample-Multiplexing. ANAL. SCI. 36, 1099–1104 (2020). https://doi.org/10.2116/analsci.20P082
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.2116/analsci.20P082