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

Abstract

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.

Mildronate (Meldonium) in professional sports – monitoring doping control urine samples using hydrophilic interaction liquid chromatography – high resolution/high accuracy mass spectrometry

“…Since January 2015, Mildronate is subject of WADA's Monitoring Program to assess its prevalence and misuse in sport, necessitating methodologies capable of measuring and confirming the presence and absence of this drug in human urine . In recent years, different assays were presented for the identification of Mildronate in human plasma and urine, while most of them were based on hydrophilic interaction liquid chromatography‐tandem mass spectrometry (HILIC‐MS/MS) …”

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

“…MEL could not be determined by ultraviolet and fluorescence spectroscopic methods without derivation by chromophore groups due to the lack of visible absorption peak in its structure . Despite this, several analytical methods were developed for determination of MEL in human urine and plasma such as liquid chromatography‐mass spectrometry (LC‐MS) , high performance liquid chromatography (HPLC) , HPLC‐mass spectrometry (HPLC‐MS) , HPLC‐tandem mass spectrometry (HPLC‐MS/MS) and capillary electrophoresis . Among these techniques, LC‐MS method needs to sample preparation techniques such as liquid‐liquid extraction or solid phase extractions; however, MEL is not easily extracted because of its low molecular mass and high polarity .…”

“…Among these techniques, LC‐MS method needs to sample preparation techniques such as liquid‐liquid extraction or solid phase extractions; however, MEL is not easily extracted because of its low molecular mass and high polarity . Although MEL could be analyzed by LC‐MS/MS method using hydrophilic interaction liquid chromatography (HILIC) column, it needed extra cost and separation efficiency decreased . Recently, HILIC with high resolution mass spectrometry (HILIC‐HRMS) was also used to screen and confirm MEL in body fluids of sportsmen .…”

Double or multiple/secondary peaks in pharmacokinetics: considerations and challenges from a bio‐analytical perspective

“…In a recent article, Pidpruzhnykov et al (2011) developed and validated an ultra-performance liquid chromatography on a hydrophilic interaction chromatography column with a tandem mass-selective detection method for the quantification of meldonium in human plasma samples and applied it for the bioequivalence testing of two drug products of meldonium. Interestingly, inspection of the plasma data indicated that double peaks or multiple peaks were distinctly observed in the plasma concentration vs time profiles of both the drug products (Pidpruzhnykov et al, 2011).…”

“…In a recent article, Pidpruzhnykov et al (2011) developed and validated an ultra-performance liquid chromatography on a hydrophilic interaction chromatography column with a tandem mass-selective detection method for the quantification of meldonium in human plasma samples and applied it for the bioequivalence testing of two drug products of meldonium. Interestingly, inspection of the plasma data indicated that double peaks or multiple peaks were distinctly observed in the plasma concentration vs time profiles of both the drug products (Pidpruzhnykov et al, 2011). In another separate report that described the development and application of a sensitive tandem mass spectrometric method for bupropion and hydroxybupropion, double or secondary peaks were observed to manifest for the major metabolite hydroxybupropion, although such peaks were not observed for bupropion, the parent compound (Parekha et al, 2011).…”