A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats

Abstract

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid–liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.

Development of Sustained Release Baricitinib Loaded Lipid-Polymer Hybrid Nanoparticles with Improved Oral Bioavailability

“…SEM images of optimised formulae B-PLN4 represents spherical shapes and with a rough surface. Rough surfaced and agglomerated particles could be seen, probably due to the melting of lipid matrix as stearin melts around 72 °C [ 52 ] ( Figure 5 ). The size of the particles was approximately identical as measured by the DLS technique.…”

Updated mini-review of the chemistry, pharmacology and validated assays for U.S. FDA approved COVID-19 therapeutic agents

“…Both reported LC-MS methods [32,33] for Baricitinib quantitation were in rat plasma; either in combination with Methotrexate over a concentration range of 0.5-250 ng/mL for both analytes, or as a single component, with 0.2 ng/mL as lower limit of quantitation. A simple spectroscopic A-max method [34] estimated Barictinib over 10-60 μg/mL in laboratory-made tablets.…”

“…Baricitinib inhibits intracellular cytokines that elevate in late cases; including interleukins-2, -6, -10, γ-interferon, and granulocyte macrophage colonystimulating factor [29][30][31] . The literature reveals two LC assay methods for its determination in rat plasma, for the drug's pharmacokinetics [32,33] . The former reported the use of LC/MS/MS for estimation of Baricitinib and Methotrexate [32] , whereas the other used UPLC [33] .…”

“…The literature reveals two LC assay methods for its determination in rat plasma, for the drug's pharmacokinetics [32,33] . The former reported the use of LC/MS/MS for estimation of Baricitinib and Methotrexate [32] , whereas the other used UPLC [33] . Recently, a UV-spectroscopic assay was developed for the pure form of the drug and in its dosage form [34] .…”

Recent Trends in Pharmaceutical Analytical Chemistry

“…Dr. El-Nahhas et al, in their interesting contribution “ A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats ”, presented quantitation data from the determination of baricitinib in rat plasma [ 5 ]. A liquid–liquid extraction procedure with two extraction solvents (n-hexane and dichloromethane) was proposed for drug isolation from biological matrices, avoiding the potential enhancement or suppression of the MS signal.…”