Development and validation of an accessible analytical method for the quantifi cation of trimetazidine dihydrochloride for research purposes

Introduction.  The methodology of pharmaceutical development provides for the preparation and analysis of experimental samples, in particular by the amount of an active substance in the dissolution/release medium. Modern spectral and chromatographic methods are used to standardize the quality of pharmaceutical substances, which significantly complicates testing samples. The development and validation of an accessible method for the spectrophotometric determination of trimetazidine dihydrochloride (TMD) is necessary to assess the release kinetics in the samples studied.

Aim. Development and validation of a spectrophotometric method for the quantitative determination of TMD.

Materials and methods. Pharmaceutical substances of TMD and excipients met the quality requirements of regulatory documents.  The certified devices, equipment and methods used complied with the requirements of the State Pharmacopoeia of the Russian Federation, 14th ed. and the recommendations of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).

Results. To develop a method for the spectrophotometric determination of TMD, the maximum absorbance was detected at 269 ± 2 nm. Due to the need to quantify the release profiles of the active substance from experimental samples (granulates and tablets) of TMD in acidic medium and phosphate buffer (pH = 6.8 ± 0.05), the method was validated under such conditions. The constructed calibration curve showed that the linear range of the method is 5.0–25.0  μ g/ml with a correlation coefficient of 0.9994 in acidic medium (HCl 0.1 M) and 10.0–50.0 μ g/ml with a correlation coefficient of 0.9997 in phosphate buffer. Such characteristics of the method as specificity, accuracy and precision were within reference limits. The determination of TMD using this method in mixture models formulated into granules and tablets showed coincidence with the reference values within the limits of acceptable deviations.

Conclusion. A spectrophotometric method for the quantitative determination of TMD within the maximum absorbance at 269 ± 2 nm was developed and validated, which makes it possible to use it during pharmaceutical development.

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