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Simultaneous Determination of Seven Neuroactive Steroids Associated with Depression in Rat Plasma and Brain by High Performance Liquid Chromatography?Tandem Mass Spectrometry

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Abstract

Sensitive and specific biomarkers are required for the diagnosis and treatment of depression because the existing diagnostic criteria are subjective and could produce false positives or negatives. Some endogenous neuroactive steroids that have shown either antidepressant effects or concentration changes in individuals with depression could provide potential biomarkers. In this study, a simple and specific method was developed to simultaneously determine seven endogenous neuroactive steroids in biological samples: cortisone, cortisol, dehydroepiandrosterone, estradiol, progesterone, pregnenolone, and testosterone. After liquid–liquid extraction, chromatographic separation was achieved on a C18 column with gradient elution using water-methanol at a flow rate of 300 μL min−1. Detection and quantitation were performed by tandem mass spectrometry with atmospheric pressure chemical ionization and selected reaction monitoring. Plasma and brain neuroactive steroid levels were then determined in control rats and rats exposed to forced swimming, a classical rodent model of depression. The results showed that the plasma concentrations of testosterone, pregnenolone, and progesterone significantly increased in rats exposed to the forced swimming test. In contrast, brain homogenate levels of cortisol, estradiol, and progesterone decreased, while pregnenolone levels were elevated in this model of depression. In conclusion, a new method to quantify neuroactive steroids was successfully developed and applied to their investigation in rat plasma and brain. The findings of this study indicated that plasma testosterone, pregnenolone, and progesterone levels could provide potential biomarkers for the diagnosis and treatment of depression.

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Acknowledgments

The authors would like to thank the School of Pharmaceutical Sciences, Sun Yat-Sen University. The authors would like to thank the Leading Talents in Entrepreneurship of Guangzhou Municipal Government (Startup Project LCY201306), the Leading Talent Project in Science and Technology of Guangzhou Development (Project No: 2013 L-p090), the South China Comprehensive Platform for New Medicine R&D (2009ZX09301-015) and the National Natural Science Foundation of China (Project No: 81302868). The authors declare no conflict of financial interests.

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Author notes

  1. Y. W. and L. T. contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, No. 40, Zhongshan 2nd Road, Guangzhou, GD, 510080, China

    Youqiong Wang, Lipeng Tang, Jiesi Chen, Tiandong Leng, Xiaoke Zheng, Wenbo Zhu, Haipeng Zhang, Pengxin Qiu, Xiaoxiao Yang & Guangmei Yan

  2. Department of Pharmacy, The First Affiliated Hospital of Guangxi University of Chinese Medicine, No. 89-9 Dongge Road, Nanning, GX, 530023, China

    Youqiong Wang

  3. Department of Pharmacology of Traditional Chinese Medicine, Guangdong Province?s Traditional Chinese Medical Hospital, No. 111 Dade Road, Guangzhou, GD, 510006, China

    Lipeng Tang

  4. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-Sen University, No. 40, Zhongshan 2nd Road, Guangzhou, GD, 510080, China

    Wei Yin

  5. School of Pharmaceutical Sciences, Sun Yat-Sen University, No. 132 Outer Ring East Road, Higher Education Mega Center, Guangzhou, GD, 510006, China

    Haiyan Hu

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  1. Youqiong Wang
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Correspondence to Haiyan Hu.

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Wang, Y., Tang, L., Yin, W. et al. Simultaneous Determination of Seven Neuroactive Steroids Associated with Depression in Rat Plasma and Brain by High Performance Liquid Chromatography?Tandem Mass Spectrometry. ANAL. SCI. 32, 981–988 (2016). https://doi.org/10.2116/analsci.32.981

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  • DOI: https://doi.org/10.2116/analsci.32.981

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