METFORMIN-SENSITIVE POTENTIOMETRIC SENSOR

Abstract

Metformin (N,N-dimethylbiguanidine) in its protonated form as metformin hydrochloride is used worldwide as an advanced antidiabetic drug for type 2 diabetes. Hyperinsulinemia and insulin resistance of cells are the main causes of this disease. For patients with diabetes, metformin hydrochloride (hereinafter – MET) works by improving cell sensitivity to insulin. It has been shown that metformin with tropeolin 00 (T00) forms an ionic associate that can be isolated in solid form and is suitable for the creation of plasticized membrane potentiometric metformin-sensitive sensors. The energy efficiency of ionic associate formation is substantiated by the method of mathematical modeling. Molecular modeling of T00- + MET+ systems and related calculations were performed using the HyperChem 8.0 package for various initial variants of counter ion relative to each other (single point procedure). Geometric optimization of ions was performed by the method of molecular mechanics MM+. The standard enthalpy (ΔH0) of ion formation and the association “MET+ + T00-” was determined by the semi-empirical method PM3. The difference in the energy of formation of the ionic associate and the sum of the energies of formation of its components is 312 kJ/mol. Therefore, the process of ionic associate formation is thermodynamically advantageous. Modeling and optimization of membrane composition is carried out. The results of the study of the influence of the nature of plasticizers on the electroanalytical properties of the developed sensors indicate that the best plasticizer for the system is TCP or DNF. For these solvents, the product of the dielectric constant and Rorschneider polarity (ε × PR) is 123,5 and 175 respectively. For plasticizers that were less effective (DBF and DEF), these values are 235,6 and 326 respectively. For membranes with the same content of plasticizer of one homologous series (DEF, DBF, DOF, DNF), the slope of the Nernst function decreases with increasing dielectric constant of the plasticizer solvent. It is shown that the working pH range of the electrode is from 2 to 11. The drift potential does not exceed 1–3 mV/day. Stable values of electrode potentials are set for 5–15 s. The stability of the electroanalytical characteristics of the optimized membranes can be traced for at least three months. The developed sensors show satisfactory selectivity in relation to a number of substances and ions. The 300 and 1000 times the amount of glucose, starch, polyvinyl alcohol, Na+, K+, Mg2+, Ca2+, Ba2+ ions do not interfere with MET determination. This, in turn, allows the practical use of developed MET-sensitive sensors in a variety of objects. A method of potentiometric determination of metformin has been developed, which has been tested in its determination in dosage forms.