Sacubitril Case Study

ABSTRACT:
LCZ696 (sacubitril/valsartan, EntrestoTM) is a novel therapy proposed for heart failure treatment. It was recently approved by the FDA in order to decrease the mortality rate and hospitalization for patients with chronic heart failure. So this study is considered as the first report to investigate the fluorimetric behavior of sacubitril in addition to pursuing all the different conditions which may affect its fluorescence. Numerous conditions were studied such as studying the effects of pH, solvents, time and organized media which may affect the fluorescence behavior of sacubitril. For the simultaneous determination of a newly approved supramolecular complex of Valsartan (VAL) and sacubitril (SAC) in their tablets, a novel, highly
For each standard solution of VAL and SAC, the emission spectra were recorded in the range 250–700 nm with excitation at 249 nm and were corrected for the blank signal, Figs. 2, 3a,3b. First derivative emission fluorimetry method (D1 method) was applied using Δλ = 2nm, Figs.3à,3b̀. The absolute values of the first derivative were measured at 448 and 300 nm for the determination of VAL and SAC, respectively, Fig.4. Absolute derivative values, at the selected points, were plotted against the corresponding concentration of each drug, to obtain the calibration graphs. After that, the corresponding regression equations for each drug were derived. The direct method of using the RFI at λem of each drug (416 and 314 nm for VAL and SAC respectively) was used for comparison with the proposed D1
The fact that each compound has its specific emission maxima without overlap from the other, allows their quantification without prior separation when they are found in equal ratio. However, when one drug is minor this method failed to determine the minor component. Therefore, the first derivative technique was chosen for simultaneous determination of both VAL and SAC in synthetic mixtures of different ratios whether they are equal or one is minor and the other is major. Different excitation wavelengths were examined to reach the most suitable one. Using the selected λex, both VAL and SAC gave a reasonable relative FI at λem 416 and 314 nm, for Val and SAC respectively. Another λex for VAL was reported [17] at 227 nm. Although this wavelength λex 227 gives higher response for VAL than λex 249 nm, it couldn’t be used as it yielded a very low and non-reproducible RFI values for SAC which will hinder the simultaneous determination of both drugs in their dosage form