MS/MS Method Validation for the Quantitative Determination of Vadadustat in In-Vitro Spiked Saliva

Abstract

Introduction: Vadadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI) developed for the treatment of anemia associated with chronic kidney disease (CKD). It mimics the body's natural response to hypoxia (low oxygen levels) by stimulating endogenous erythropoietin (EPO) production, thereby increasing red blood cell (RBC) levels.

Objectives: To prevent frequent blood withdrawal during bio analysis,there is a necessity to develop convenient method for patients.So far there are no existing methods for determination of the same in in-vitro saliva by LC-MS/M which rapid in estimation.

Methods: The max of Vadadustat was observed at 245 nm by UV spectrometry establishing a very good linearity along with sensitivity. The detection limit (LOD) =0.2845µg mL-1 and quantitation limit (LOQ)= 0.9013 μg mL-¹ were obtained from the linear concentrations taken in the range of 1.5-15 µg mL-1. The correlation coefficient (r2) of 0.999 was found. The method validation parameters according to ICH Q2 (R1) were performed.

Results: The developed method described here UPLC-MS/MS method was found to be novel, sensitive and rapid with improved results when successfully tested for human saliva samples without significant differences in the steady state Vadadustat concentrations.

Conclusions: Current method could answer the safety issues during therapeutic drug monitoring and pharmacokinetic behavior of the drug when tested clinically.