Quantification of desloratadine in human plasma by LC-ESI-MS/MS and application to a pharmacokinetic study

Abstract

A simple, sensitive, and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the quantification of desloratadine (DL) in human plasma using desloratadine-d5 (DLD5) as an internal standard (IS). Chromatographic separation was performed using an Xbridge C18 column (50 mm×4.6 mm, 5 μm) with an isocratic mobile phase composed of 10 mM ammonium formate: methanol (20:80, v/v), at a flow rate of 0.7 mL/min. DL and DLD5 were detected with proton adducts at m/z 311.2→259.2 and 316.2→264.3 in multiple reaction monitoring (MRM) positive modes, respectively. Liquid-liquid extraction (LLE) method was used to extract the drug and the IS. The method was validated over a linear concentration range of 5.0-5000.0 pg/mL with a correlation coefficient of (r²)≥0.9994. This method demonstrated intra- and inter-day precision within 0.7-2.0% and 0.7-2.7%, and an accuracy within 101.4-102.4%, and 99.5-104.8%. DL was found to be stable throughout the freeze-thaw cycles, bench-top, and postoperative stability studies. This method was successfully applied in the analysis of plasma samples following oral administration of DL (5 mg) in 35 healthy Indian male human volunteers under fasting conditions.

Keywords: Bioequivalence; Desloratadine; Mass spectrometry; Pharmacokinetic study.

Figure 1

Chemical structures of desloratadine and desloratadine-D5.

Figure 2

(A) Parent ion mass spectra of desloratadine and (B) product ion mass spectra of desloratadine.

Figure 3

(A) Parent ion mass spectra of desloratadine-D5 and (B) product ion mass spectra of desloratadine-D5.

Figure 4

MRM chromatogram of blank human plasma.

Figure 5

Chromatogram of desloratadine, desloratadine-D5 at LOQ level.

Figure 6

Mean plasma concentrations of test vs. reference after a 5 mg dose (one 5 mg Tablet) single oral dose (35 healthy volunteers).