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Post heroin dose tissue distribution of 6-monoacetylmorphine (6-MAM) with MALDI imaging

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Abstract

Heroin is an illicit opioid drug which is commonly abused and leads to dependence and addiction. Heroin is considered a pro-drug and is rapidly converted to its major active metabolite 6-monoacetylmorphine (6-MAM) which mediates euphoria and reward through the stimulation of opioid receptors in the brain. The aim of this study was to investigate the distribution and localization of 6-MAM in the healthy Sprague Dawley rat brain following intraperitoneal (i.p) administration of heroin (10 mg/kg), using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), in combination with quantification via liquid chromatography mass spectrometry (LC–MS/MS). These findings revealed that 6-MAM is present both in plasma and brain tissue with a Tmax of 5 min (2.8 µg/mL) and 15 min (1.1 µg/mL), respectively. MSI analysis of the brain showed high intensities of 6-MAM in the thalamus-hypothalamus and mesocorticolimbic system including areas of the cortex, caudate putamen, and ventral pallidum regions. This finding correlates with the distribution of opioid receptors in the brain, according to literature. In addition, we report a time-dependent distribution in the levels of 6-MAM, from 1 min with the highest intensity of the drug observed at 15 min, with sparse distribution at 45 min before decreasing at 60 min. This is the first study to use MSI as a brain imaging technique to detect a morphine’s distribution over time in the brain.

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Acknowledgements

The authors would like to thank the National Research Foundation, SA; Aspenpharmacare, SA; and the University of KwaZulu-Natal, Durban, SA for having funded this project.

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Authors and Affiliations

  1. Catalysis and Peptide Research Unit, School of Health Sciences, University of KwaZulu-Natal, E-block, 6th floor, Room E1-06-016, Westville Campus, Durban, 4000, South Africa

    Belin G. Teklezgi, Annapurna Pamreddy, Sooraj Baijnath, Tricia Naicker, Hendrik G. Kruger & Thavendran Govender

  2. Department of Criminology, University of KwaZulu-Natal, Durban, South Africa

    Nirmala D. Gopal

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  1. Belin G. Teklezgi
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  2. Annapurna Pamreddy
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  3. Sooraj Baijnath
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  4. Nirmala D. Gopal
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  5. Tricia Naicker
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  6. Hendrik G. Kruger
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  7. Thavendran Govender
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Correspondence to Thavendran Govender.

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Teklezgi, B.G., Pamreddy, A., Baijnath, S. et al. Post heroin dose tissue distribution of 6-monoacetylmorphine (6-MAM) with MALDI imaging. J Mol Hist 48, 285–292 (2017). https://doi.org/10.1007/s10735-017-9726-3

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  • DOI: https://doi.org/10.1007/s10735-017-9726-3

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