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Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry

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Abstract

Background and Objectives

Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB.

Methods

The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS after a single intragastric administration (50 to 450 mg/kg) in mice, and samples were collected from five animals at specific time points.

Results

Pharmacokinetic parameters of MDHB following intragastric administrations were: the time to peak concentration (Tmax) ranged from 0.033 to 0.07 h, the peak concentration (Cmax) ranged from 12,379.158 to 109798.712 μg/l, the elimination half-life (t1/2z) ranged from 0.153 to 1.291 h, the area under the curve (AUC0–∞) ranged from 640.654 to 20,241.081 μg/l × h, the mean residence time (MRT0–∞) ranged from 0.071 to 0.206 h, the apparent volume of distribution (Vz/F) ranged from 17.538 to 45.244 l/kg, and the systemic clearance (Clz/F) ranged from 22.541 to 80.807 l/h/kg. The oral bioavailability of MDHB was 23%. The maximum MDHB content was detected in the stomach, and the minimum content was observed in the testes; the peak content in the brain was 15,666.93 ng/g.

Conclusions

The pharmacokinetic characteristics of MDHB include fast absorption, high systemic clearance, a short half-life and an oral bioavailability of 23%. Additionally, MDHB permeates the blood-brain barrier (BBB) and is rapidly distributed to all organs. The identification of the pharmacokinetics of MDHB following its oral administration will contribute to further preclinical and clinical studies of its effects.

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Author information

Author notes

  1. Jia Hui Wang, Song Hui Hu and Ji Yan Su contributed equally to this study.

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China

    Jia Hui Wang, Song Hui Hu, Jun Ping Pan, Xiang Nan Mi, Chao Fen Su & Huan Min Luo

  2. State Key Laboratory of Applied Microbiology Southern China, Guangdong Institute of Microbiology, Guangzhou, China

    Ji Yan Su

  3. School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China

    Hai Ju Geng

  4. Department of Pathogen Biology and Medical Immunology, School of Basic Medicine, Ningxia Medical University, Yinchuan, China

    Wei Zhang

  5. School of International Education, Anhui Medical University, Hefei, China

    Liang Cai

  6. Analytical and Testing Center, Jinan University, Guangzhou, China

    Ai Hua Hong

  7. Institute of Brain Sciences, Jinan University, Guangzhou, China

    Huan Min Luo

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  1. Jia Hui Wang
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Corresponding author

Correspondence to Huan Min Luo.

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Funding

This work was supported by grants from the National Natural Science Foundation Committee of China (grant nos. 81473296, 81173037 and 81202519), the National Program on Key Basic Research Project (973 Program; no. 2011CB707500) and the Guangdong Provincial Department of Science and Technology (grant nos. 2012B050300018 and 2010B030700018).

Conflict of Interest

None of the authors have conflicts of interest to declare.

Ethical Approval

The animal experiments adhered to the “Jinan University Medical College Animal Use Ordinance” and were approved by the Ethics Committee of the Medical School of Jinan University.

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Wang, J.H., Hu, S.H., Su, J.Y. et al. Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry. Eur J Drug Metab Pharmacokinet 44, 237–249 (2019). https://doi.org/10.1007/s13318-018-0512-8

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