Quantification and pharmacokinetic assessment of SB225002 in mouse: a selective non-peptide CXCR2 antagonist

SB225002 was a selective non-peptide antagonist of CXC Chemokine Receptor 2 (CXCR2), but its detection method in mass spectrometry and pharmacokinetic (PK) parameters in mouse were not reported.

Following methanol-induced protein precipitation and centrifugation, the analyte was separated using an Agilent ZORBAX SB-C18 column (2.1 mm × 100 mm, 3.5 μm, Agilent, MA, USA) with an isocratic mobile phase comprising 25% methanol (phase A) and 75% water containing 0.3% formic acid (phase B). The mobile phase was delivered at a flow rate of 0.3 mL/min. The PK of SB225002 were assessed in a mouse model.

SB225002 demonstrated a strong linear relationship in range of 20.00 to 4000.00 ng/mL, with recovery between 96.9% and 99.6%, and matrix effects ranging from 98.9% to 104.6%. SB225002 demonstrated acceptable short-term, long-term, and freeze-thaw stability, with all other items meeting the requirements. The method was utilized to assess PK of SB225002 in mouse, revealing rapid absorption (t_max: 0.4 ± 0.1 h, mean±SD) and metabolism (t_1/2: 3.4 $\pm$ 2.6 h), along with significant inter-individual variability.

This study successfully developed and validated a UHPLC-MS/MS method to determine SB225002 in mouse plasma and first reported its pharmacokinetic parameters in mouse, potentially facilitating further clinical research.