Studying the suitability of hybrid micelle liquid chromatography for estimating the lipophilicity of some partial dopamine agonists used to attain the reward circuit.

M E K Wahba,D El Sherbiny,D El Wasseef

doi:10.1098/rsos.202371

Abstract

Three micellar-based mobile phases were developed and optimized for the simultaneous determination of certain partial dopamine agonists that are used to overcome the withdrawal symptoms of abused drugs, namely aripiprazole, pramipexole and piribedil. The studied drugs were separated using micellar liquid chromatography, hybrid micellar liquid chromatography (HMLC) and microemulsion liquid chromatography (MELC). The three developed mobile phases were studied to estimate their suitability for the measurement of log p-values of the studied drugs. Experimental determination of log Pm/w values using the three mobile phases demonstrates that HMLC is the mobile phase of choice since the obtained practical log Pm/w values were in accordance with the reported log P values, and calculated log P and log D values. An explanation of the obtained results was presented based on the separation retention mechanism for each chromatographic technique. Furthermore, the effect of the pH and the column temperature in HMLC on the practical log Pm/w values was studied. To verify its suitability for experimental measurement of log Pm/w , HMLC was subjected to full validation according to the United States Pharmacopeia.

Highlights

Amphetamine, methamphetamine and cocaine are ranked by the world drug report [1] as the most prevalent psycho-stimulant illicit abused drugs
The reward circuit, a terminology referring to the enhancement of dopamine secretion in the meso-limbic portion of the brain, is intimately connected to behavioural reinforcement [2,3,4,5], while this effect is not induced by elevation in the concentration of other neurotransmitters; noradrenaline and serotonin [6,7,8]
A detailed investigation was carried out to study the suitability of hybrid micellar liquid chromatography (HMLC) for the practical determination of log P of three selected partial dopamine agonists (PDA) used to attain the reward circuit

Summary

Introduction

Amphetamine, methamphetamine and cocaine are ranked by the world drug report [1] as the most prevalent psycho-stimulant illicit abused drugs Their CNS-stimulating effect is produced by increasing the synaptic concentration of neurotransmitters like dopamine, noradrenaline and serotonin [2]. The idea of using partial dopamine agonists (PDA) as therapeutic agents to overcome the withdrawal symptoms of drug abuse has been supported by examination in drug addiction animal models [9]. The rationale for this unique therapeutic effect arises from the fact that PDA possesses high affinity but low inherent activity for dopamine receptors. A significant impact of structure–activity relationship (SAR), based mainly on chemical structure and physico-chemical properties of PDA, imparts this unique pharmacological behaviour to such pharmaceutical compounds [8,9,10]

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Conclusion