Design Approach in RP-HPLC Method Development and Validation of Nirogacestat in its Pure and Pharmaceutical Dosage Form

Abstract

Aim: Nirogacestat is a selective γ-secretase inhibitor approved by the USFDA for the treatment of Desmoid Tumour.

Objective: In this study, a reversed-phase high performance liquid chromatography (RP-HPLC) method was designed to analyze the concentration of Nirogacestat in both bulk and dosage forms.

Method: With a 30 % Trifluoroacetic acid pH3:70 % Acetonitrile (30:70 ml) mobile phase, 1.2 ml/min flow rate, 338 nm detection wavelength, 10 µl injection volume, and 12-minute run time, a SPURSIL C18-EP (4.6 x 250mm, 5µm) column was utilized. The experiment was designed using the Box-Behnken design (BBD), and the chromatographic conditions flowrate, buffer pH and buffer ratio were optimized by applying the response surface methodology (RSM). After evaluating separation response metrics such tailing factor and retention time to develop an optimization model, the desirability was assessed.

Result: The model indicated that a composite desirability of 0.9943 could be attained with a flowrate of 0.80 mL/min-1, a buffer pH of 4, and a buffer ratio of 30. The theoretical plate and tailing factor of the improved HPLC settings were all within acceptable limits.

Conclusion: The current research was found to be observed with less Rt and this method can be a suggested approach for the development of new techniques in pharma industries.