Development and validation of a novel stability‐indicating reverse phase HPLC method for the determination of sacubitril–valsartan premix stereoisomers: Cellulosetris(4‐methyl benzoate) stationary phase

Abstract

A new stability indicating reverse phase HPLC method has been developed and validated as per International Conference on Harmonization guidelines for the determination of sacubitril-valsartan premix stereoisomers, namely, (2R)valsartan, (2S,4S)-sacubitril, (2R,4S)-sacubitril, and (2R,4R)-sacubitril. Primarily, stability indicating separation study was done on reverse phase LC conditions; it was described by peak homogeneity of sacubitril-valsartan and its stereoisomers. Cellulose tris(4-methylbenzoate) packing column Chiralcel OJ-RH(150 mm × 4.6 mm), 5 μm provided better resolution than those of amylose based stationary phase's. Resolution between two arbitrary adjacent analyte was found to be more than 2.0 with 0.1% trifluoroacetic acid in water as mobile phase-A and mobile phase-B consisting of acetonitrile, methanol, and trifluoroacetic acid (90:10:0.1, v/v/v). Gradient elution was performed at a flow rate of 1.0 ml/min, column temperature 20 • C, injection volume 10 μl, UV detection at 254 nm and run time was 52 min. The detector response linearity of stereoisomers found to be linear (R 2 ≥ 0.9998), limit of detection (0.290 μg/ml, 0.122 μg/ml, 0.123 μg/ml, and 0.124 μg/ml), and limit of quantification (0.878 μg/ml, 0.370 μg/ml, 0.373 μg/ml, and 0.375 μg/ml), respectively. Percentage recovery was found to be 98-105. Finally, the proposed method is user friendly and can be used in bulk drugs analysis.

Liquid chromatographic determination of lumacaftor in the presence of ivacaftor and identification of five novel degradation products using high‐performance liquid chromatography ion trap time‐of‐flight mass spectrometry

“…Another important point is that SIM is specific or selective. It is the determination of active pharmaceutical ingredient (API) in the presence of excipients, additives, and degradation products that are expected to be present in the specific SIM [9,10]. Selective SIM is the technique that measures API and all degradation products in the presence of excipients and additives [9,11,12].…”