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Rapid, sensitive and simultaneous determination of fluorescence-labeled designated substances controlled by the Pharmaceutical Affairs Law in Japan by ultra-performance liquid chromatography coupled with electrospray-ionization time-of-flight mass spectrometry

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Abstract

A simultaneous determination method based on ultra-performance liquid chromatography (UPLC) with fluorescence (FL) detection and electrospray-ionization time-of-flight mass spectrometry (ESI-TOF-MS) was developed for 16 “designated substances” (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan. These substances were first labeled with 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole at 60 °C for 2 h in 0.1 M borax (pH 9.3). The resulting fluorophores were well separated by reversed-phase chromatography using an Acquity UPLC™ BEH C18 column (1.7 μm, 100 mm × 2.1 mm i.d.) by isocratic elution with a mixture of water and acetonitrile–methanol (20:80) containing 0.1% formic acid. The separated derivatives were sensitively detected by both FL and TOF-MS. However, the determination of several designated substances by FL detection showed interference from endogenous substances in biological samples. Therefore, the determination in real samples was carried out by a combination of UPLC separation and ESI-TOF-MS detection. The structures of the designated substances were identified from the protonated-molecular ions [M+H]+ obtained from the TOF-MS measurement. The calibration curves obtained from the peak area ratios of the internal standard (I.S.), i.e., 3-phenyl-1-propylamine, and the designated substances versus the injection amounts showed good linearity. The limits of detection \( \left( {{\text{S/N}} = 3} \right) \) and the limits of quantification \( \left( {{\text{S/N}} = 10} \right) \) in 0.1 mL of human plasma and urine for the present method were 0.30–150 pmol and 1.0–500 pmol, respectively. Good accuracy and precision (according to intraday and interday assays) were also obtained with the present procedure. This method was applied to analyses of human plasma, urine and real products.

Structures of designated substances tested

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Acknowledgment

The present research was supported in part by a Health Sciences Research Grant from the Ministry of Health Labor and Welfare in Japan, and a Research Grant from the Ministry of Education, Science, Sports and Culture of Japan.

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Authors and Affiliations

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

    Jun Zhe Min, Suguru Hatanaka, Toshimasa Toyo’oka & Shinsuke Inagaki

  2. Division of Pharmacognosy, Phytochemistry and Narcotics, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo, 158-8501, Japan

    Ruri Kikura-Hanajiri & Yukihiro Goda

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  1. Jun Zhe Min
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  2. Suguru Hatanaka
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  3. Toshimasa Toyo’oka
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  4. Shinsuke Inagaki
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  5. Ruri Kikura-Hanajiri
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  6. Yukihiro Goda
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Correspondence to Toshimasa Toyo’oka.

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Min, J.Z., Hatanaka, S., Toyo’oka, T. et al. Rapid, sensitive and simultaneous determination of fluorescence-labeled designated substances controlled by the Pharmaceutical Affairs Law in Japan by ultra-performance liquid chromatography coupled with electrospray-ionization time-of-flight mass spectrometry. Anal Bioanal Chem 395, 1411–1422 (2009). https://doi.org/10.1007/s00216-009-3046-8

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  • DOI: https://doi.org/10.1007/s00216-009-3046-8

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