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Microsomal stability

SL Seung-Hee Lee
VV Vimal Veeriah
FL Fred Levine
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Microsomal stability studies were performed in the Conrad Prebys Center for Chemical Genomics. In vitro metabolism was conducted in a system consisted of NADPH generating system, test compound, and Tris·Cl buffer. The mixture was pre-incubated at 37 °C for 30 min. Reactions were initiated by addition of mouse or human liver microsomes suspension and shaken at 37 °C with air exposure. To generate the stability curve for the test compound, the incubation was terminated at 0, 5, 15, 30 and 60 min. NFT and NCT concentrations were determined by LC-MS. The result of metabolic stability was expressed as the percentage of compound remaining at 1 hr. The in vitro half-life (t1/2) and intrinsic clearance (Clint) were calculated based on drug depletion over incubation time.

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