Aim and Objective::
An analytical method for the determination of mobocertinib, an investigational tyrosine kinase inhibitor, was
developed and optimized by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat plasma.
Materials and Methods::
Plasma samples were pretreated by the protein precipitation method with a methanol solution of osimertinib as the
internal standard (IS). Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, I.D. 5 μm) column
with the temperature maintained at 40 °C. The mobile phase consisted of water (containing 0.1% formic acid) and methanol in a gradient
mode at a flow rate of 0.5 mL/min. Mass spectrometric detection was carried out in the selected reaction monitoring (SRM) mode with positive
electrospray ionization, and the mass transitions of mobocertinib and osimertinib were m/z 587.01 → 71.88 and m/z 499.80 → 71.94,
respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability
and carryover as per the guidelines for bioanalytical method validation (FDA, 2018). The method was applied to the pharmacokinetic
study of mobocertinib in rats by oral gavage at the doses of 2, 6, and 18 mg/kg. A total of 216 plasma samples from 18 rats were analyzed.
Results::
It showed good linearity over the range of 1-1000 ng/mL (R2 = 0.9957). The intra-batch accuracy was within 94.65-102.59% and
the precision was within 5.49-10.46%. The inter-batch accuracy was within 97.08-102.25% with a precision of 7.54-10.13%. The extraction
recovery and matrix factor were acceptable for the bioanalysis of mobocertinib. Additionally, mobocertinib was found to be stable under the
detected conditions. Mobocertinib showed linear pharmacokinetic characteristics following oral administration to rats at 2.0-18.0 mg/kg.
Conclusion::
The developed and validated method was successfully employed in the pharmacokinetic study in rats following oral administration
of mobocertinib at the doses of 2, 6, and 18 mg/kg.
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