Kinetic Analysis by HPLC-Electrospray Mass Spectrometry of the pH.Dependent Acyl Migration and Solvolysis as the Decomposition Pathways of Ifetroban l-O-Acyl Glucuronide

摘要

The decomposition of both α- and β-anomers of ifetroban 1-O-acyl glucuronide in an aqueous medium was studied at ambient temperature (23℃). An HPLC/MS technique was used to investigate the decomposition of these anomers via hydrolysis and acyl migration over a pH of 1.0-13.0. It was found that while no acyl migration occurred at pH≤4.0, hydrolysis occurred at both acidic and basic pH. The hydrolysis rate was the slowest the pH range of 3.0-4.0. Outside this range, the tale d hydrolysis increased as the pH was increased or decreased. The acyl migration at pH 5.0 was very slow, but the rate increased as the pH was increased. First-order rate constants (in h↑(-1)), as a function of pH, were estimated according to a simplified scheme for both hydrolysis and acyl migration processes. Methanolysis of the β-anomer was studied in 80% or 100% methanol in water and also in 20% methanol in aqueous buffer solutions with apparent pH values of 3.0, 6.0 and 9.0. A systematic study alt varying the pH and ionic strength of the HPLC mobile phase showed that both .parameters significantly affected the resolution and retention times of the positional isomers and anomers. The HPLC method developed was capable of separating all the positional isomeric glucuronides and their anomers.