Determination of Histamine H3-Receptor Antagonist Conessine in Wistar Rat Plasma by a Rapid and Sensitive RP-UFLC Method: Application to a Pharmacokinetic Study

    Published on:April 2020
    Journal of Young Pharmacists, 2020; 12(1):55-62
    Original Article | doi:10.5530/jyp.2020.12.11

    Nilesh Sudhakar Ambhore1,*, Rama Satyanarayana Raju Kalidhindi1, Shubhashri Mohire2, Karthik Yamjala2, Shashank Mulukutla1, Vishakantha Murthy4, Mahesh Thondawada3, Kannan Elango1

    1Department of Pharmacology, JSS College of Pharmacy, Ootacamund (JSS University), Tamil Nadu, Ooty, INDIA.

    2Department of Pharmaceutical Analysis, JSS College of Pharmacy, Ootacamund (JSS University), Ooty, Tamil Nadu, INDIA.

    3Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, Ootacamund (JSS University), Ooty, Tamil Nadu, INDIA.

    4Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA.


    Objectives: Epidemiological data suggests the highest density of histamine H3-receptors (H3R) in basal ganglia of central nervous system (CNS) wherein they function as inhibitory auto-receptors and control the release of many neurotransmitters. Inhibition of H3R increases the turnover of neurotransmitters, especially dopamine in basal ganglia and could be beneficial to treat Parkinson’s disease. Methods: In this study, we formulated the brain targeting liposomes of conessine, a selective antagonist for H3R to increase bioavailability and developed and validated a rapid and sensitive reverse phase ultra-force liquid chromatographic (RP-UFLC) method and to quantitate conessine in Wistar rat plasma and tissue. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and aripiprazole as the internal standard. Chromatographic separation was performed on the Hibar C18 column with a mobile phase of Hexane Sulphonic acid (10 mM, pH 10.0 adjusted with ammonia) and methanol at a flow rate of 0.9 ml/min. Results: The lower limit of quantification of the developed method was 4.0 ng/ml and 6.0 ng/g in plasma and tissue samples, respectively. Liposomes of conessine (equivalent to 20 mg/kg) administered orally to animals, demonstrated remarkable absorption into the systemic circulation with maximum concentration (~8700 ng/ ml) within 2.0 h. The order of area under curve was found to be kidney> brain> liver> lungs> spleen> heart. Conclusion: The liposomes of conessine were rapidly taken up into the brain and showed a good brain concentration after 2.0 h; sustenance up to 4.0 h was achieved which is better than conessine solution.

    Key words: Conessine, RP-UFLC method, Pharmacokinetic, Tissue distribution, Validation.

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