Electrochemical Sensor for Selective Detection of Meldonium in Urine by Voltammetry

A highly sensitive electrochemical sensor based on arenediazonium tosylates was designed to detect meldonium in urine. The effect of the concentration of ArN2⁺OTs⁻ arenediazonium tosylate modifier and various substituents was studied. Basic operating parameters for voltammetric meldonium detection were established and the procedure for urine sample preparation was developed. The following values were obtained: limit of detection (LOD) 0.005 mg ⋅ L⁻¹ (P=0.95) and limit of quantification (LOQ) 0.01 mg ⋅ L⁻¹. The relationship between the analytical signal and meldonium concentration in the solution ranging from 0.01 to 400 mg ⋅ L⁻¹ was described by a linear function. The meldonium concentration error did not exceed 18 %. The analysis time for a single urine sample was reduced to 15 minutes.     

UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium

A rapid and simple method based on ultra-performance liquid chromatography on a hydrophilic interaction chromatography column with tandem mass-selective detection (UPLC-MS/MS) to determine meldonium in human plasma was developed. The calibration curve acquired in the range of 10-6000 ng/mL had quadratic form. Method validation proved the conformity of its properties (selectivity, matrix effect, lower limit of quantification, accuracy, precision and recovery) with the established requirements. The stability tests necessary for bioanalytical studies were performed. For the first time, the method was successfully applied to the bioequivalence studies of generic and brand name oral drugs of meldonium in capsules. Based on data from 24 volunteers, it was determined that the mean pharmacokinetic curves of the drugs are characterized by a double peak profile.     

Electrosynthesis of Molecularly Imprinted Poly‐o‐phenylenediamine on MWCNT Modified Electrode for Selective Determination of Meldonium

In this study, a molecularly imprinted polymer (MIP) was synthesized by electrochemical polymerization and used to construct an electrochemical sensor for determination of meldonium (MEL) selectively for the first time. The polymer film was generated by using o‐phenylenediamine (o‐PD) as a monomer on the surface of carboxylic acid functionalized multiwalled carbon nanotube (MWCNT) modified pencil rod electrode in the presence of MEL as a template. MEL imprinted (MEL‐imp) and non‐imprinted (N‐imp) polymer films and coated electrodes were characterized by Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), profilometry, electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Voltammetric measurements were carried out in a ferrocyanide/ferricyanide redox probe solution for MEL‐imp and N‐imp electrodes in the presence and absence of template molecule. The decrease in peak current of redox probe was linear with the concentration of MEL in the range of 0.1–5 μg/mL and the limit of detection (3 s/b) was found to be 0.066 μg/mL under optimized experimental conditions. The proposed sensor was successfully applied for selective determination of MEL in human urine sample with long term stability and good reproducibility.