DEVELOPMENT AND VALIDATION OF REVERSE PHASE-HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY TECHNIQUE FOR THE CONCOMITANT ASSESSMENT OF OMEPRAZOLE AND PIPERINE IN BULK FORM

Objective: The immense literature study was carried out and disclosed that here no method arrived for the concomitant assessment of omeprazole and piperine in bulk form by using RP-HPLC. Hence, an effort was assembled to arise a easy, specific, precise, reliable, linear, rapid, and validated reverse phase-high-performance liquid chromatography (RP-HPLC) technique for the simultaneous assessment of omeprazole and piperine in bulk form.Methods: The chromatographic analysis of omeprazole and piperine was performed using a RP-HPLC (WATERS) provided with autosampler and ultraviolet (UV) detector with the software of EMPOWER Version 2. The chosen conditions were isocratic separation with two mobile phase composed of acetonitrile:buffer (phosphate buffer: pH 6.5 ± 0.1) (55:45). Detection was carried out using UV/visible double-beam spectrophotometer at 320 nm. The method was validated as per the ICH guidelines.Results: The retention time for omeprazole and piperine by proposed HPLC method was found to be 2.767 and 4.029 min, respectively. The correlation coefficients are 0.999. The developed chromatographic method was found to be accurate with recovery 99.2–99.8% and was found within the acceptance criteria (i.e., 98.0–102.0%) with acceptable % relative standard deviation of not >2% at each level.Conclusion: Thus, the proposed HPLC procedure for the concomitant assessment of omeprazole and piperine was accurate, precise, linear, robust, simple, and economic.Â

Theoretical

Molecular modeling studies were carried out on a series of benzimidazole and imidazo[1,2-a]pyridines as Plk1 inhibitors. Based on the pharmacophore model, we obtained a five-featured hypothesis AADRR, with two hydrogen bond acceptors, one hydrogen bond donor and two aromatic rings. An atom-based 3D-QSAR model was predicted for 36 training set (R2 = 0.9475, SD = 0.1927, F = 99.3) and nine test set (Q2 = 0.6519, RMSE = 0.4044, Pearson R = 0.834) compounds using a pharmacophore-based alignment. From these results, AADRR pharmacophore feature was chosen as the best common pharmacophore hypothesis, whereas the atom-based 3D-QSAR results explain the importance of hydrophobic and electron-withdrawing features for the most active compound 32. The dataset molecules were docked into the active site of Plk1, which shows acceptable hydrogen bond interactions with residues Cys133, Asp194, Glu131, Lys82 and Glu140 and also shows further hydrogen bond interactions with hydrophobic residues Cys67, Leu59 and Arg136. These results can be helpful for further design of novel Plk1 inhibitors