| Digoxin is the most important secondary cardiotonic glycoside of Digitalis lanata Ehrh.,which is used for the treatment of acute and chronic congestive cardiac arrest and supraventricular arrhythmia.As one of the commonly prescribed Narrow Therapeutic Index(NIT)drugs,digoxin overdose can lead to a series of heart diseases.High purity digoxin standard material is the guarantee to ensure the accuracy and traceability of digoxin detection results.In order to improve medication safety and ensure that the blood concentration of digoxin was within the safe range of treatment,the purification and the accurate determination technology of digoxin were studied in this paper.The solubility of digoxin in three kinds of pure solvents(ethanol,methanol,isopropanol),two kinds of binary mixed solvents(methanol+water,ethanol+water)and one kind of ternate mixed solvent(ethanol+solvent A+water)was determined by equilibrium method in the temperature range of 278.15~323.15 K.The solubility data of digoxin was correlated with modified Apelblat equation,polynomial equation and ?h equation.And thermodynamic data of enthalpy and entropy of solution were calculated with Van't Hoff equation.The experimental results showed that the solubility of digoxin added with the increase of temperature,At the same temperature,the solubility of digoxin in the ternary mixed solvent was the highest,and the solubility in 20% ethanol-water was the lowest.The results of thermodynamic theoretical analysis showed that the enthalpy of solution was positive,indicating that the dissolution process of digoxin in the selected solvents was endothermic.The purification of digoxin raw materials were carried out by using the fractional dissolution method and solvent crystallization method respectively.The effects of solvent type,dissolution time,dissolution series and solid-liquid ratio were investigated in the process of fractional dissolution.And the factors such as crystallization solvent,temperature,cooling rate,stirring rate and solid-liquid ratio were investigated in the solvent crystallization purification process.Under the optimal operating conditions,the purity of digoxin product reached to 99.51%(HPLC).Qualitative analysis of digoxin product was carried out by liquid-mass spectrometry(LC-MS),infrared spectroscopy(IR)and nuclear magnetic resonance spectroscopy(NMR),and the impurity components of digoxin product were identified.Digoxin product was analyzed by mass balance method and the purity was 99.20%. |
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