DOI: https://doi.org/10.15587/2519-4852.2018.141397

Development and validation of spectrophotometric method for the determination of meldonium dihydrate in dosage forms

Аnastasiia Donchenko, Natalia Nahorna, Svitlana Vasyuk

Abstract


Aim. Spectrophotometry is one of the most widely used methods in the pharmaceutical analysis. The main advantages of this absorption method are the highly sensitive, cost-effective and available to quality control laboratories for dosage forms. However, there is a need to find new analytical reagents. Therefore, the aim of the present work was investigation and development of spectrophotometric method based on reaction with p-chloranil for the determination of meldonium dihydrate in dosage forms.

Methods. In the study were used working standard of meldonium dihydrate, p-chloranil, DMF, the sample of finished dosage forms. Absorption of the reaction products was measured using spectrophotometer Specord 200.

Results. The optimum conditions of the spectrophotometric analysis has been established during the process of development this procedure. The influence of various parameters such as nature of the solvent, concentration of reagent, temperature, time of heating were investigated. It was experimentally established that meldonium dihydrate reacts with p-chloranil in DMF medium to form the coloured reaction product with absorption maximum at 556 nm. The proposed method was subjected to validation tests. The method was validated for the parameters like linearity, precision, accuracy, robustness and range of application. Beer’s law was performed at the concentration range of 8.00-20.00 mg/100 ml with correlation coefficient 0.9995. The linearity ranges were calculated with the help of regression analysis by means of least squares. The proposed procedure meets the requirements of State Pharmacopoeia of Ukraine.

Conclusions. The spectrophotometric method for the determination of meldonium dihydrate was developed and validated. This procedure is successfully applied for dosage forms analysis. Results of the study showed that the procedure is accurate, simple and relevant for application at the quality control laboratories for dosage forms


Keywords


spectrophotometry; derivatives of quinone; p-chloranil; meldonium dihydrate; analysis; quantitative determination; validation

Full Text:

PDF

References


Prykhodko, Yu. V., Kashkovskyi, D. O., Prykhodko, V. M. (2015). Metabolichna terapiia v praktytsi simeinoho likaria. Znachennia metabolichnykh preparativ v heriatrychnii klinitsi [Metabolic therapy in medical general practice. Metabolic drugs in geriatrics]. Semeynaya meditsina, 1 (57), 7–16.

Gorbunova, A. A., Kireev, S. Yu., Rashevskaya, I. V. (2017). Mel'doniy: svyaz' stroeniya, struktury i svoystv [Meldonium: connection of structure, structure and properties]. Vestnik Penzenskogo gosudarstvennogo universiteta, 2 (17), 92–99.

Dzerve, V., Kalvinsh, I. (2013). Mildronat v kardiologii. Obzor issledovaniy [Mildronate in cardiology. Research Overview]. Riga, 76.

MEL'DONIY (MELDONIUM). Opisanie aktivnykh veshhestv. Spravochnik Kompendium. Available at: https://compendium.com.ua/akt/77/2984/meldonium/

Gosudarstvennaya farmakopeya Rossiyskoy Federatsii. XII-izd. [State Pharmacopoeia of Russian Federation. 12th ed.] (2008). Moscow: Izdatel'stvo «Nauchnyy tsentr ekspertizy sredstv meditsinskogo primeneniya», 704.

European Pharmacopoeia. 8.3th ed. (2015). Strasbourg: European Department for the Quality of Medicines, 4378.

Peng, Y., Yang, J., Wang, Z., Wang, J., Liu, Y., Luo, Z., Wen, A. (2010). Determination of mildronate by LC–MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers. Journal of Chromatography B, 878 (5-6), 551–556. doi: http://doi.org/10.1016/j.jchromb.2009.12.030

Pidpruzhnykov, Y. V., Sabko, V. E., Iurchenko, V. V., Zupanets, I. A. (2011). UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium. Biomedical Chromatography, 26 (5), 599–605. doi: http://doi.org/10.1002/bmc.1703

Gavrilin, M. V., Mudretsova, Yu. V., Senchenko, S. P., Rozhnova, S. A. (2012). Razrabotka metodiki kolichestvennogo opredeleniya kholina al'fostserata i mel'doniya metodom kapillyarnogo elektroforeza [Development of quantification method for determination of choline alphoscerate and meldonium by capillary electrophoresis]. Voprosy biologicheskoy, meditsinskoy i farmatsevticheskoy khimii, 4, 12–17.

Derzhavna Farmakopeia Ukrainy. Vol. 1 [State Pharmacopoeia of Ukraine. Vol. 1] (2015). Kharkiv: Derzhavne pidpryiemstvo «Naukovo-ekspertnyi farmakopeinyi tsentr», 1128.

Ermer, J. (2015). Method Validation in Pharmaceutical Analysis: A Guide to Best Practice. Weinheim: Wiley-VCH., 440.

Grizodub, A. I. (2016). Standartizovannye protsedury validatsii metodik kontrolya kachestva lekarstvennykh sredstv [Standardized procedures for the validation of drug quality control methods]. Kharkiv: Gosudarstvennoe predpriyatie «Ukrainskiy nauchnyy farmakopeynyy tsentr kachestva lekarstvennykh sredstv», 396.


GOST Style Citations


Prykhodko Yu. V., Kashkovskyi D. O., Prykhodko V. M. Metabolichna terapiia v praktytsi simeinoho likaria. Znachennia metabolichnykh preparativ v heriatrychnii klinitsi // Semeinaia medytsyna. 2015. Issue 1 (57). P. 7–16.

Gorbunova A. A., Kireev S. Yu., Rashevskaya I. V. Mel'doniy: svyaz' stroeniya, struktury i svoystv // Vestnik Penzenskogo gosudarstvennogo universiteta. 2017. Issue 2 (17). P. 92–99.

Dzerve V. Ya., Kalvinsh I. Ya. Mildronat v kardiologii. Obzor issledovaniy. Riga, 2013. 76 p.

MEL'DONIY (MELDONIUM). Opisanie aktivnykh veshhestv // Spravochnik Kompendium. URL: https://compendium.com.ua/akt/77/2984/meldonium/

Gosudarstvennaya farmakopeya Rossiyskoy Federatsii. XII-izd. Moscow: Izdatel'stvo «Nauchnyy tsentr ekspertizy sredstv meditsinskogo primeneniya», 2008. 704 p.

European Pharmacopoeia. 8.3th ed. Strasbourg: European Department for the Quality of Medicines, 2015. 4378 p.

Determination of mildronate by LC–MS/MS and its application to a pharmacokinetic study in healthy Chinese volunteers / Peng Y. et. al. // Journal of Chromatography B. 2010. Vol. 878, Issue 5-6. P. 551–556. doi: http://doi.org/10.1016/j.jchromb.2009.12.030 

Pidpruzhnykov Y. V., Sabko V. E., Iurchenko V. V., Zupanets I. A. UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium // Biomedical Chromatography. 2011. Vol. 26, Issue 5. P. 599–605. doi: http://doi.org/10.1002/bmc.1703 

Razrabotka metodiki kolichestvennogo opredeleniya kholina al'fostserata i mel'doniya metodom kapillyarnogo elektroforeza / Gavrilin M. V. et. al. // Voprosy biologicheskoy, meditsinskoy i farmatsevticheskoy khimii. 2012. Issue 4. P. 12–17.

Derzhavna Farmakopeia Ukrainy. Vol. 1. Kharkiv: Derzhavne pidpryiemstvo «Naukovo-ekspertnyi farmakopeinyi tsentr», 2015. 1128 p.

Ermer J. Method Validation in Pharmaceutical Analysis: A Guide to Best Practice. Weinheim: Wiley-VCH., 2015. 440 p.

Grizodub A. I. Standartizovannye protsedury validatsii metodik kontrolya kachestva lekarstvennykh sredstv. Kharkiv: Gosudarstvennoe predpriyatie «Ukrainskiy nauchnyy farmakopeynyy tsentr kachestva lekarstvennykh sredstv», 2016. 396 p.







Copyright (c) 2018 Аnastasiia Donchenko, Natalia Nahorna, Svitlana Vasyuk

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

ISSN 2519-4852 (Online), ISSN 2519-4844 (Print)