Abstract
Aim: A simple and rapid HPLC technique was developed and validated to simultaneously estimate enzalutamide (ENZ) and repaglinide (REP) in rat plasma.Methods: In silico predictions using DDinter and DDI-Pred indicated possible drug-drug interactions between ENZ and REP. A central composite design was used to identify factors influencing the separation of the drugs. Interactions between chromatographic parameters were studied through 51 experiments, followed by illustration with three-dimensional response surface plots. The four factors optimized for the separation of the two drugs are column temperature (A), % organic strength (B), pH (C) and column type (D).Results: Plate count(R1), tailing factor (R2) and resolution (R3) responses in the experimental design were analyzed with the favorable chromatographic conditions predicted to be 0.1% formic acid and acetonitrile as mobile phases on a Phenomenex C18 LC column (250×4.6mm, 5μm). The method was applied to estimate the drugs in rat plasma using a simple protein-precipitation step and found to be linear, accurate and precise within the ranges of 0.5-16 and 5-50μg/ml for ENZ and REP, respectively.Conclusion: The optimized method can be used in future bioanalytical workflow for drug quantification and drug-drug compatible studies.
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