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High performance liquid chromatographic determination of YJC-10592, a new chemokine receptor 2 (CCR-2) antagonist, in biological samples

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Abstract

YJC-10592, a new chemokine receptor 2 (CCR-2) antagonist, was newly synthesized for the treatment of asthma and atopic dermatitis. To evaluate the pharmacokinetic characteristics of YJC-10592, a high-performance liquid chromatographic (HPLC) method was developed for the determination of YJC-10592 in rat plasma, urine, and tissue homogenates, using YJC-10450 as an internal standard. The mobile phase was a gradient of acetate buffer (50 mM, pH 3.0) in acetonitrile at a flow rate of 1.0 mL/min. Chromatograms were monitored by an ultraviolet detector at 230 nm. The retention times for YJC-10592 and the internal standard were 8.0 and 6.3 min, respectively, and the lower limits of quantification (LLOQ) for YJC-10592 in rat plasma and urine were 0.05 and 0.2 μg/mL, respectively. The intra- and inter-assay precisions (coefficients of variation, CVs) were generally low (below 11.4 %) for rat plasma and urine samples. The accuracies (relative errors) ranged from 94.2 to 108 %. No interferences from endogenous substances were found. YJC-10592 was stable in rat whole blood but unstable in the liver homogenate. An initial pharmacokinetic study was performed in Sprague–Dawley rats and demonstrated that YJC-10592 has a half-life of 86.8 min and wide tissue distribution. In summary, this HPLC method can be applied to future preclinical and clinical evaluation of YJC-10592.

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Acknowledgments

This work was supported by the Gyeonggi Provincial R&D Projects (C1212) funded by the Gyeonggi Institute of Science & Technology Promotion (GSTEP), Republic of Korea and the Korea Health Technology R&D Project (HI16C0992) through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea.

Conflict of interest

All authors (Du ES, Moon HS, Lim SJ, Chang SY and Kim SH) declare that they have no conflict of interest.

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Authors and Affiliations

  1. College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 443-749, Republic of Korea

    Eun Sin Du, Sun Young Chang & So Hee Kim

  2. Yang-Ji Chemical Company, Suwon, Republic of Korea

    Hong Sik Moon

  3. Department of Bioscience and Biotechnology, Sejong University, Seoul, Republic of Korea

    Soo-Jeong Lim

Authors
  1. Eun Sin Du
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  2. Hong Sik Moon
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  3. Soo-Jeong Lim
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  4. Sun Young Chang
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  5. So Hee Kim
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Correspondence to So Hee Kim.

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Du, E.S., Moon, H.S., Lim, SJ. et al. High performance liquid chromatographic determination of YJC-10592, a new chemokine receptor 2 (CCR-2) antagonist, in biological samples. Journal of Pharmaceutical Investigation 46, 495–504 (2016). https://doi.org/10.1007/s40005-016-0257-9

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  • DOI: https://doi.org/10.1007/s40005-016-0257-9

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