Bioanalytical Method Development and Validation of 2-(4-Ethoxyphenyl Sulphonamido) Pentane-Diamide, a Novel Antitumor and Antiangiogenic Agent, in Rat Serum and Application of the Method in Determination of Pharmacokinetic Parameters

Abstract

Objective: The present study focuses on the development and validation of a bioanalytical method for the quantification of 2-(4-ethoxyphenyl sulphamido) pentane-diamide, a candidate antitumor and antiangiogenic agent, in rat serum. The developed method was subsequently applied to determine the pharmacokinetic parameters of the compound. Methods: To quantify the compound and determine its pharmacokinetic properties in rats, a liquid chromatography-mass spectrometry (LC-MS) bioanalytical method has been developed and the pharmacokinetic parameters were computed by compartmental model analysis. Results: A linear relationship was detected within the concentration range of 10 to 5000 ng/ml prepared by adding standard solutions of the test compound to the pooled serum of 10 SD rats, which exhibits high levels of precision, accuracy, and reproducibility. An appreciable recovery in the range of 97.20±0.63 to 93.22±1.48 percent was determined, with no noticeable impact from the matrix. The pharmacokinetic parameters, namely oral absorption rate constant (Ka) (5.054±0.238 1/h), elimination rate constant (KE) (2.585±0.357 h), volume of distribution (V) (8.173±0.333 L/kg), and bioavailability of (73.2%), were determined by the utilization of PK-solver software. Conclusion: We developed a simple yet precise and validated LC-MS method to analyze the drug candidate in rat serum. Simple protein precipitation and extraction were cost-effective. This bioanalytical approach was successful due to its good linearity, high recoveries, no matrix influence, and matrix stability. PK solver derived I. V. and oral pharmacokinetics parameters from the best-fit one-compartment model. Because of its high oral absorption, biological half-life, and bioavailability, the compound is suitable for oral administration.