The PI3K/AKT/MTOR signalling pathway plays an important role in the growth and
proliferation of tumour cells. N-((3S,4S)-4-(3,4-Difluorophenyl)piperidin-3-yl)-2-fluoro-4-(1-methyl-
1H-pyrazol-5-yl)benzamide (Hu7691) is a new-generation selective AKT inhibitor developed at
Zhejiang University. In this study, we developed an ultra-performance liquid chromatographytandem
mass spectrometry (UPLC-MS/MS) for the measurement of Hu7691 in dog plasma. Plasma
was precipitated with acetonitrile and then separated on a trifunctionally bonded alkyl column.
Excellent separation efficiency and selectivity were achieved by adjusting the mobile phase ratio,
with a total running time of only 5 min. The linear dynamic range of the calibration curve was
5–1000 ng/mL. The method was fully validated, and all performance metrics met the criteria. The
validated method was used for the pharmacokinetic monitoring and bioavailability assessment of
Hu7691 in dogs. The results showed that the area under the curve and peak plasma concentration
of Hu7691 increased with increasing dose (oral 5, 10, 20 mg/kg, intravenous 10 mg/kg), and oral
bioavailabilities were 86.7%, 50.8%, and 50.5%, respectively, indicating a high bioavailability of
Hu7691 in dogs. This provides a test basis for the clinical application of the compound.
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