UDC 615.073/.074:615.27:615.453.4:543.48:547.673.5

The aim of the work was to develop a simple, rapid, economic spectrophotometric method for the determination of meldonium in capsules based on the reaction with alizarin.
Materials and methods. Analytical equipment: double-beam UV-visible spectrophotometer Shimadzu UV 1800 (Japan), a pair of 1 cm matched quartz cells, software UV-Probe 2.62, laboratory electronic balance RAD WAG AS 200/C, pH-meter I-160МI. Pharmacopoeial standard sample (CRS) of meldonium dihydrate (Sigma-Aldrich, (≥98 %, HPLC)), alizarin (Synbias), capsules Metamax (Darnytsia) 250 mg, Vasopro (Farmak) 500 mg, Mildronate (Grindex) 500 mg, dimethylformamide (“Honeywell Riedel-de Haen”).
Results and discussion. A spectrophotometric method for determining meldonium in capsules by reaction with alizarine has been developed. The absorption maximum of the formed complex in dimethylformamide was at a wavelength of 517 nm. Stoichiometric ratios of reactive components «meldonium- alizarin» were 1:1. Validation of the developed analytical method for the determination of meldonium in medicines was carried out in accordance with the requirements of the SPhU. The optimal conditions for performing the quantitative determination of meldonium have been established: concentration of alizarin solution – 0.8 %, volume 0.8 % alizarin solution – 0.5 ml, heating time – 20 min, temperature – 95±2 °C. Linearity has been in the concentration range of 0.0402–0.1073 mg/mL, the limit of detection – 2.84 μg/mL, and the limit of quantification – 8.59 μg/mL. The eco-friendliness of the developed analytical method was carried out using the analytical eco-scale, AGREE, and GAPI methods.
Conclusions. The developed method can be used as an arbitration method for the routine analysis of meldonium capsules

New 4-aryl-3-(morpholin-4-yl)-2-arylimino-2,3-dihydrothiazole derivatives 1.1-1.16 were obtained using the Hantzsch reaction by condensation of N-(morpholin-4-yl)-N'-arylthioureas with the corresponding α bromoacetophenones in alcohols. Synthesized hydrobromides 1.1-1.8 were formed as crystalline precipitates during the boiling of the reaction mixture. Bases 1.9-1.16 were obtained by neutralizing the corresponding hydrobromides with NH₄OH solution. It has been proposed a possible mechanism of the reaction that is based on the study of the structure of the synthesized compounds. The structures of the synthesized compounds were confirmed by ¹H NMR spectroscopy with its special techniques (NOESY and ROESY experiments). It has been shown the formation of the isomer 4-(4'-chlorophenyl)-3-(morpholin-4-yl)-2-(4'-chlorophenylamino)-2.3-dihydrothiazole on the basis of compound 1.14. Pharmacological screening of synthesized derivatives of 4-aryl-2-arylimino-2,3-dihydrothiazole compounds revealed the analgesic effect in the model of visceral pain caused by the introduction of acetic acid to white mice. The anti-inflammatory effect of the synthesized compounds was evaluated in vivo by reducing limb edema in rats with carrageenan-induced inflammation. Thus, the synthesized compounds have analgesic and anti-inflammatory activity.

Keywords: COVID-19; ascorbic acid; copper; fat-soluble vitamins; iron; magnesium; micronutrients; selenium; vitamin B complex; zinc..