Interfacial behaviour and quantitative analysis of hexadecyl phosphocholine drug at a polarized liquid/liquid interface

Abstract

The interfacial behaviour of the amphiphilic drug hexadecyl phosphocholine (HePC, also called miltefosine) was analysed by cyclic voltammetry applied at the water/1,2-dichloroethane interface. HePC is the only oral drug currently approved for the treatment of visceral, mucosal  and cutaneous leishmaniasis. Because of its amphiphilic character, it can interact with biological membranes, solubilizing their compounds and leading to cell disruption. These interactions are responsible for its side effects and toxicity; therefore, HePC quantification in biological fluids and pharmaceutical preparations is extremely important. However, the lack of a chromophore in its structure prevents its spectroscopic determination. For this reason, the main challenge of this work was to propose an electroanalytical method for the quantification of this drug, which constitutes a simpler alternative than liquid chromatography-tandem mass spectrometry already reported. With this aim, in the first part of this work, the mechanism of the electrochemical process occurring after polarizing the interface was studied. By varying the experimental conditions, it was possible to determine that in a first step, at open circuit or at low potential values, HePC spontaneously adsorbed to the interface. Later, as the potential increased, the transfer of the anions present in the organic phase towards the aqueous side of the interface, where the HePC polar head groups were present, occurred thus forming adsorbed “ion pairs” and producing an increase in positive current. Subsequently, in the negative sweep, the “ion pairs” dissociated and desorbed giving rise to a negative peak. In this way, both negative and positive currents were considered useful for quantitative purposes. In the second part of this work, an appropriate experimental procedure was designed and proposed as a quantitative methodology for the HePC determination, which consisted of cleaning the interface and controlling the time at open circuit, followed by the voltammetric analysis. A linear response of both, positive or negative, peak currents with drug concentration was obtained within an acceptable range, providing a simple solution for the HePC quantification problem. Future studies will be carried out to evaluate the quantification and selectivity in real matrices containing polymer micelles working as HePC nanocarriers with the aim of avoiding the adverse effects of HePC when it is orally or intravenously administered.