APPLICATION OF VALIDATED LC-MS/MS METHOD FOR THE QUANTIFICATION OF LENVATINIB IN BIOLOGICAL MATRICES: SUPPORTING IN-VIVO BIOAVAILABILITY STUDIES IN HEALTHY RABBITS

摘要

A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was developed and validated for the quantification of lenvatinib in plasma samples. Plasma samples were presented by selecting the Liquid-Liquid extraction (LLE) method with ethyl acetate. The technique was developed and validated with respect to the parameters specificity, sensitivity, carry-over, recovery, precision, matrix effect, accuracy, and stability. The lenvatinib and IS (lenvatinib-D4) were eluted within 3.5 min on Symmetry-C 18 column (50 mm × 4.6mm × 5μm) with 0.1% V/V formic acid in acetonitrile, methanol, and 0.1% V/V formic acid in water in the ratio of 70:20:10 as mobile phase with 0.70 ml/min infusion flow rate. This analytical method was also applied successfully to study bio-availability studies in 6 healthy rabbits. LVB was shown T max of 3.452 ± 0.754, mean C max of 89 ± 3.045 , AUC 0?t of 1700.01 ± 257.892, and AUC 0?t of 3665.3 ± 259.59 for Test formulation. The method can be useful in the quantification of lenvatinib in clinical research organizations for bioavailability studies and in forensic studies.