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- W2068741437 abstract "PAC-14028 ((E)-N-((R)-1-(3,5-difluoro-4-methanesulfonylamino-phenyl)-ethyl)-3-(2-propyl-6-trifluoromethyl-pyridine-3-yl)-acrylamide) is a novel and potent transient receptor potential vanilloid type I (TRPV1) antagonist. We developed and validated a rapid, sensitive and selective liquid chromatography/tandem mass spectrometric method for determination of PAC-14028 in rat and minipig plasma. After protein precipitation PAC-14028 and internal standard (methylated analog, PAC-14026) were separated on a Symmetry C18 column (4.6 mm × 75 mm, 3.5 μm) with an isocratic mobile phase, acetonitrile: water (8:2, v/v) containing 0.2% formic acid and monitored by electrospray positive ionization with multiple reaction monitoring mode (PAC-14028, 492 → 156; IS, 506 → 156, m/z). The calibration curve was linear over the range of 1.0–500 ng/ml (r2 > 0.999) and lower limit of quantitation (LLOQ) was 1 ng/ml. The precision and accuracy were within ±15% and the stability was acceptable during bench-top, auto-sampler, 3 freeze–thaw cycles and 4-week storage in a freezer at −80 °C. This method was successfully applied to the intravenous, oral and topical pharmacokinetic studies of PAC-14028 in rats and minipigs, which showed comparable pharmacokinetic parameters (T1/2, 2.1 h and 3.8 h; F%, 52.7% and 64.2% for rats and minipigs, respectively). Percutaneous absorption of PAC-14028 was negligible after topical application (F% 0.2–1.7%)." @default.
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- W2068741437 date "2012-03-01" @default.
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- W2068741437 title "Oral and topical pharmacokinetic studies of a novel TRPV1 antagonist, PAC-14028 in rats and minipigs using liquid chromatography/tandem mass spectrometric method" @default.
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- W2068741437 doi "https://doi.org/10.1016/j.jpba.2011.11.011" @default.
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