High performance thin-layer and high performance liquid chromatography coupled with photodiode array and fluorescence detectors for analysis of valsartan and sacubitril in their supramolecular complex with quantitation of sacubitril-related substance in raw material and tablets.

Valsartan (VAL) and sacubitril (SAC) are combined in a supramolecular complex, LCZ696, which is a newly approved remedy for heart failure. SAC-related substance (biphenyl methyl pyrrolidinone [BMP]) which also appears as an intermediate during SAC synthesis is considered to be a suspected impurity for SAC and/or LCZ696 tablets. The study investigates the analysis of VAL and SAC in their supramolecular complex along with SAC-related substance, BMP, using high performance thin-layer chromatography (HPTLC) and high performance liquid chromatography (HPLC) with two different detectors; fluorescence detector (FLD) and diode array detector (DAD). The work aimed at analyzing BMP at low levels in the presence of its parent drug, SAC. BMP was successfully analyzed at a level of 0.167, 1 and 3% of its parent drug, SAC upon using HPLC-FLD, HPLC-DAD and HPTLC, respectively. For HPLC-FLD, the detector was set at λex/λem (nm/nm): 0-4.5 min at 255/374; 4.5-6 min at 255/314, for achieving an adequate sensitivity of the method to monitor and quantify VAL and SAC in the presence of BMP. Low limits of detection (8.3, 3.3 and 1.7 ng mL-1) and limits of quantitation (25, 10 and 5 ng mL-1) values obtained for VAL, SAC and BMP, respectively, upon using FLD suggest that low level of baseline noise enables the detection and quantitation of low BMP concentration.