A sensitive, heart-cutting, two-dimensional liquid chromatography–tandem mass spectrometry method for the determination of mometasone furoate in human plasma: Application for a bioequivalence study in nasal spray formulations

Abstract

We developed and validated a sensitive, heart-cutting, two-dimensional liquid chromatography–tandem mass spectrometry (2D-LC‒MS/MS) method to determine the concentration of mometasone furoate in human plasma after nasal spray administration. Isotopically labeled mometasone furoate-13C,d6 was used as an internal standard (IS). Plasma samples were prepared using a solid-phase extraction (SPE) method. With this 2D-LC strategy, the analytes were trapped in the first dimension (1D) column, and only judiciously selected portions of the 1D effluent were transferred to the second dimension (2D) column for further separation to obtain high-resolution information. MS/MS quantification was performed in positive ionization mode via multiple-reaction monitoring (MRM). This analytical method was fully validated according to related regulatory guidance, and the results showed that the method is robust and sensitive enough for pharmacokinetic investigation of mometasone furoate with satisfactory linearity from 0.25 to 30 pg mL−1. This method was successfully applied to a bioequivalence (BE) study of mometasone furoate aqueous nasal sprays in healthy volunteers.