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

Abstract

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.

Application of a white and green spectrofluorimetric approach for facile quantification of amlodipine, a hypotensive drug, in batch materials, dosage forms, and biological fluids; content homogeneity testing

“…The unique pharmacokinetic and pharmacodynamic characteristics of AMD seem to be linked to its physicochemical features, particularly its high degree of ionization and basicity [14]. Several methods have been conducted to determine AMD alone and with other drugs in its pure form and commercial samples: the redox titrimetric method [15], spectrophotometric methods [16][17][18], spectrofluorimetric methods [17,[19][20][21][22][23][24][25][26][27][28], high-performance liquid chromatography [29][30][31][32], thin layer chromatography [30], electroanalytical methods [31,33], and capillary electrophoretic methods [34,35]. Kokilambigai et al have provided a good review of the different analytical methods for determining AMD [36].…”

Development and validation of a stability‐indicating, single HPLC method for sacubitril–valsartan and their stereoisomers and identification of forced degradation products using LC–MS/MS

“…This method is capable of separating only process‐related impurities but not the enantiomers. RP‐HPLC method (Ragab et al, 2018) used a Zorbax Eclipse plus C18 column (250 × 4.6 mm, 2 μm); the mobile phase was ACN and 25‐mM monobasic sodium phosphate buffer, pH 3.0 (35:35) v/v. This method is not capable of quantifying enantiomers, and this method does not discuss forced degradation studies.…”

“…propionate hemicalcium, its molecular formula is C 24 H 28 NO 5 .0.5Ca 2+ , and its molecular weight is 430.52 g/mol (Figure 1). In the literature different types of methods are reported for the determination of sacubitril, valsartan, and their impurities, such as HPLC methods (Attimarad et al, 2018;Dongala et al, 2021;Ettaboina et al, 2021;Francotte et al, 1996;Hafez et al, 2013;Jyothi & Umadevi, 2018; F I G U R E 1 Chemical structures of sacubitril-valsartan complex and their five impurities Katakam et al, 2021;Lee et al, 2015;Lu et al, 2018;Moussa et al, 2018;Phalguna et al, 2018;Ragab et al, 2018;Rane et al, 2009;Sampatha et al, 2009;Subramanian et al, 2022;Tatar & Sa glík, 2002;Yenda et al, 2021), spectrophotometric methods (Eissa & Abou Al Alamein, 2018;Ragab et al, 2017;Youssef et al, 2021), ultra-high-performance liquid chromatography (Katakam et al, 2020;Prajapati et al, 2020), LC-MS/MS (Chunduri & Dannana, 2016;Katakam et al, 2021;Shah et al, 2009;Shah et al, 2017), and capillary electrophoresis (Alnajjar, 2011). The HPLC normal-phase method (Lu et al, 2018) used n-hexane:ethanol:isopropyl alcohol (92:6:2) as diluent; sacubitril-valsartan tablets are not soluble in this diluent.…”

“…This method is capable of separating only process-related impurities but not the enantiomers. RP-HPLC method (Ragab et al, 2018) This method is not suitable for finished products. It is a normal-phase method, and diluent was n-hexane: EtOH:IPA (92:6:2).…”

Stability‐indicating reversed‐phase‐HPLC method development and validation for sacubitril/valsartan complex in the presence of impurities and degradation products: Robustness by quality‐by‐design approach

“…SCB and VLS tablets in the rat plasma method (Mahesh et al, 2018) do not exhibit the stability-indicating nature and are not applicable for quality control stability analysis. Further, the reported high-performance thinlayer chromatography method (Marwa et al, 2018) estimates SCB and VLS in drug and drug products, but this method does not discuss the forced degradation studies. All these methods use chromatographic conditions, and the details are provided in Table 1.…”