Application of salts of chaotropic anions in the development of hplc methods for the determination of meldonium in dosage forms

Abstract

The aim of the work was to create an approach for the development of HPLC methods for the determination of meldonium in dosage forms with the usage of salts of chaotropic anions in mobile phases. Material and methods. Analytical equipment: Shimadzu UPLC system LC-40 PDA; Shimadzu Nexera-i LC-2040C 3D-Plus, controlled by software Lab Solution version 5.97, electronic laboratory balance RAD WAG AS 200/C, pH-meter I-160MI. Meldonium dihydrate (purity 99.3 %) was purchased from Sigma-Aldrich (Switzerland), and Vasopro capsules 500 mg were purchased from a local pharmacy. Chromatographic conditions: Agilent Zorbax C-18 SB 150 mm x 4.6 mm 3.5 μm column was used (Agilent Technologies, USA). Mobile phases: 1) 0.25 % KPF6 w/v – 0.1 % v/v 85 %H3PO4 95 % – 5 % ACN, 2) 0.3 % bis-(trifluoromethane)sulfonimide lithium salt 97 % w/v – 0.1 %v/v 85 % H3PO4 80 % – 20 % acetonitrile. Flow rate - 1mL/min, T=32 °C, detection UV=at 4 channels - 190 nm, 195 nm, 200 nm, 205 nm. Results and discussion. We have proposed two approaches using two different salts of chaotropic anions - potassium hexafluorophosphate and bis-(trifluoromethane)sulfonimide lithium salt – for the HPLC method development. The chaotropic effects of these anions toward meldonium strongly influenced the analyte migratory behaviour. Both mobile phases involved, in addition to the use of a chaotrope, also the use of acetonitrile and pH adjustment with 0.1 % v/v 85 % H3PO4 solution. The detection wavelength (190 nm, 195 nm, 200 nm, 205 nm) was selected experimentally. The results were obtained for 8 concepts. Parameters of the chromatographic system confirm the conclusions and results of this investigation for the influence of chaotropic salts on N-containing molecules in an acidic pH medium, by increasing their retentivity and improving peak shape and uniformity homogeneity, even on the column without end-capping and base-deactivating. Validation of the analytical method was carried out following the requirements of SPhU. Conclusions. HPLC methods for the determination of meldonium in dosage forms have been developed, using positive impacts of chaotropic salts on the molecules containing N-atoms in their molecule on their retentions and peak symmetries on the chromatogram. The validation of the analytical methods showed their suitability for pharmaceutical analysis