Anatase titanium oxide nanoparticles and multi-walled carbon nanotubes-modified carbon paste electrode for simultaneous determination of avanafil and doxorubicin in plasma samples

Abstract

Patients who receive anticancer drugs, might experience loss of sexual desire together with erectile dysfunction as one of cancer medications’ adverse effects. This might have a negative effect on their psychological functioning and quality of life and accordingly phosphodiesterase type 5 (PDE5) inhibitors as sex stimulants are used. One of the recently FDA-approved members of this class of drugs is avanafil (AVN) that is administered to assist in improving penile erection. Because of the seriousness of the cancer patient's health condition, it is mandatory to recognize the possible pharmacokinetic interactions in case of administering other drugs at the same time. Therefore, a sensitive sensor derived from carbon paste electrode (CPE) modified with anatase titanium dioxide nanoparticles (TiO2-NPs) and multi-walled carbon nanotubes (MWCNTs) was designed for the simultaneous determination of AVN and the anticancer drug doxorubicin (DOX) in spiked and real rabbit plasma samples. X-ray powder diffraction (XRD), Fourier transform infrared (FT-IR), and scanning electron microscopy (SEM) were employed to fully characterize the fabricated electrode. The modified electrode offers a considerable improvement in voltammetric sensitivity toward oxidation of AVN and DOX, compared to the bare electrode. A good separation was achieved between the oxidation peak potentials of AVN (1.4 V) and DOX (0.8 V). The effect of different voltammetric parameters on the peak separation and sensitivity for both drugs was studied to select the optimum experimental conditions. It was found that the optimum pH for the simultaneous determination of both drugs was obtained utilizing a Britton-Robinson buffer (BR) of pH 3.0. Furthermore, the electrochemical oxidation of AVN and DOX was evaluated with different modified carbon paste electrodes using cyclic voltammetry (CV) and square-wave adsorptive anodic stripping voltammetry (SWAdASV). The analytical curves for the quantitative simultaneous determination of AVN and DOX exhibited acceptable linearity within the concentration range from (0.10–6.0 μmol L−1 for AVN) and (5.0–35.0 μmol L−1 for DOX) in spiked rabbit plasma. Detection and quantitation limits were determined to be 0.035 and 0.10 μmol L−1 in the case of AVN and 1.3 and 4.0 μmol L−1 in the case of DOX, respectively. The method was effectively applied for the analysis of AVN in real rabbit plasma samples after the coadministration of DOX. Moreover, the proposed voltammetric method was useful as a therapeutic drug monitoring method to investigate the possible pharmacokinetic interactions between AVN and DOX in real rabbit plasma. An increase in the level of AVN in rabbit plasma was observed after administering DOX, and accordingly, the dose of AVN should be adjusted and monitored.