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The direct analysis of drug distribution of rotigotine-loaded microspheres from tissue sections by LESA coupled with tandem mass spectrometry

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Abstract

The direct analysis of drug distribution of rotigotine-loaded microspheres (RoMS) from tissue sections by liquid extraction surface analysis (LESA) coupled with tandem mass spectrometry (MS/MS) was demonstrated. The RoMS distribution in rat tissues assessed by the ambient LESA-MS/MS approach without extensive or tedious sample pretreatment was compared with that obtained by a conventional liquid chromatography tandem mass spectrometry (LC-MS/MS) method in which organ excision and subsequent solvent extraction were commonly employed before analysis. Results obtained from the two were well correlated for a majority of the organs, such as muscle, liver, stomach, and hippocampus. The distribution of RoMS in the brain, however, was found to be mainly focused in the hippocampus and striatum regions as shown by the LESA-imaged profiles. The LESA approach we developed is sensitive enough, with an estimated LLOQ at 0.05 ng/mL of rotigotine in brain tissue, and information-rich with minimal sample preparation, suitable, and promising in assisting the development of new drug delivery systems for controlled drug release and protection.

Workflow for the LESA-MS/MS imaging of brain tissue section after intramuscular RoMS administration

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Acknowledgements

This work was supported by the State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies and was funded by a Work for Others Agreement with Wen-Yan Wang Laboratories, Yantai University. The authors gratefully acknowledge the financial supports by the China National High Tech R&D Program (“863” Project, 2014AA020902) and technical assistance in LESA operations by Dr. Daniel Eikel from Advion, Inc.

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Authors and Affiliations

  1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, China

    Li-Xiao Xu, Yin-Yin Geng, Wen-Yan Wang & Wan-Hui Liu

  2. State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Shandong Luye Pharmaceutical Co. Ltd., Laishan District, Yantai, Shandong, 264003, China

    Li-Xiao Xu, Tian-Tian Wang, Wen-Yan Wang & Wan-Hui Liu

  3. Naval Aeronautical and Astronautical University, Yantai, Shandong, 264001, China

    Yin Li

  4. ASPEC Technologies, Beijing, 100101, China

    Xiao-Kun Duan, Bin Xu & Charles C. Liu

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  1. Li-Xiao Xu
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  2. Tian-Tian Wang
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  3. Yin-Yin Geng
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  4. Wen-Yan Wang
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  5. Yin Li
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  7. Bin Xu
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  9. Wan-Hui Liu
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Corresponding author

Correspondence to Wan-Hui Liu.

Ethics declarations

All animal experiments were conducted in accordance with the guidelines of the Ministry of Health of People's Republic of China and the Animal Care Committee of China Medical University. The study protocol was approved by the Experimental Animal Research Committee of Yantai University.

Conflict of interest

The authors declare no competing financial interests and have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript, apart from those disclosed. The authors declare that they have no financial conflict of interest.

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Xu, LX., Wang, TT., Geng, YY. et al. The direct analysis of drug distribution of rotigotine-loaded microspheres from tissue sections by LESA coupled with tandem mass spectrometry. Anal Bioanal Chem 409, 5217–5223 (2017). https://doi.org/10.1007/s00216-017-0440-5

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  • DOI: https://doi.org/10.1007/s00216-017-0440-5

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