Molecular imprinted polymer-based potentiometric approach for the assay of the co-formulated tetracycline HCl, metronidazole and bismuth subcitrate in capsules and spiked human plasma.

Background: An anti-H-pylori co-formulated mixture of tetracycline HCl (TET), metronidazole (MET), and bismuth subcitrate (BSC) is recently available. Only two chromatographic and spectrophotometric methods are reported for determining those drugs simultaneously where the effect of impurities that could be present as well as the biological fluids matrix influence do not be taken into consideration. There is a need to develop an easy-to-use potentiometric technique for analysis of TET, MET, and BSC in their co-formulated capsules, in presence of some official impurities and in spiked human plasma.

Results: Three carbon paste electrodes (CPEs) were fabricated for this purpose. Being a solid contact ion-selective electrode, CPE suffers from the creation of a water layer affecting its stability and reproducibility. Besides, it has a common problem in differentiation between two drugs carrying the same charge (positively charged TET and MET). Water layer formation was prevented through inserting polyaniline nanoparticles (≈10.0 nm diameter) between solid contact and ion-sensing membrane in the three proposed sensors. TET and MET interference was overcome by synthesizing a corresponding molecular imprinted polymer (MIP) for each drug. The synthesized MIPs were inserted in equivalent sensing membranes and characterized using several techniques. The suggested MIPs have a noticeable enhanced sensitivity in potentiometric determination. The obtained LODs were 5.88 × 10, 5.19 × 10, and 1.73 × 10 M for TET, MET and BSC proposed CPEs, respectively, with corresponding slopes of 57.37, 56.20, and -57.40 mV decade.

Significance: The proposed potentiometric method makes the detection of the three cited drugs simple, fast, and feasible. This approach is the first for determining three drugs potentiometrically in one combined formulation. The obtained results were compared favorably with previously reported potentiometric methods.