Novel microfabricated solid-contact potentiometric sensors doped with multiwall carbon-nanotubes for simultaneous determination of bisoprolol and perindopril in spiked human plasma

Abstract

The main concern when developing solid contact ion selective electrodes is the choice of ion sensing membranes while keeping in mind, cost effectiveness, simplicity, potential stability, and reproducibility of results. The main aim of this work is to design microfabricated solid contact ion selective electrodes (SC-ISEs) for the selective determination of bisoprolol (BIS) and perindopril (PER) either in their combined pharmaceutical formulation or simultaneously in human plasma. The obstacle was improving the detection limit of the proposed microfabricated sensors so they can determine the plasma peak concentrations of both drugs. Two factors were considered, namely the addition of ionophores and doping the ion sensing membranes with multiwalled carbon nanotubes (MWCNTs). Four sensors were developed for BIS while two other sensors were developed for PER, and their electrochemical performance was assessed. Selectivity of the sensors was determined in presence of some degradation products, impurities and metabolites of BIS and PER. Doping the ion sensing membranes with MWCNTs proved to interfere with the formation of water layer, resulting in more stable performance. Furthermore, addition of calix[6]arene (CX6) increased the sensitivity in case of BIS sensor. The optimum results for BIS were obtained with ion sensing membrane of potassium tetrakis(4-chlorophenyl)borate, CX6 and MWCNTs. Whereas an ion sensing membrane of tetradodecylammonium bromide and MWCNTs, showed best response in case of PER. The linearity range obtained in case of BIS was 8 × 10−9–1 × 10−2 M with an LOD of 1.74 × 10−9M. While for PER, the linearity range was 1 × 10−8–1 × 10−2 M with an LOD of 9.12 × 10−9 M.