The F value of 2-CdA after oral administration was approximately 37% and there were no cumulative differences in bioavailability observed on multiple dosing of the drug. The absorption and disposition characteristics of oral 2-CdA were linear and predictable with this dosing regimen.

No abstract

No abstract

1. In vitro metabolism of the antiprogestin drug mifepristone (RU-486) was studied after incubation with rat, monkey and human hepatic S9 fractions in the presence of an NADPH-generating system. 2. Unchanged mifepristone (approximately 45% of the sample(s) in rat; approximately 70% in monkey; approximately 65% in human) plus six metabolites, three known and three new, were profiled, quantified and tentatively identified on the basis of MS and MS/MS data. 3. The proposed metabolic pathways for mifepristone are proposed, and the two metabolic steps are (A) N-demethylation and (B) methyl oxidation. 4. Step A formed N-desmethyl mifepristone (M1) in major amounts (approximately 35% s in rat, 16% in monkey and human) and N,N-didesmethyl mifepristone (M2) in minor amounts (< 5% s in all species). Step B, or in conjunction with step A, produced four minor/trace metabolites, namely hydroxymethyl mifepristone (M3), hydroxymethyl M1 (M4), hydroxymethyl M2 (M5) and formyl mifepristone (M6).

Electrospray mass spectrometry and tandem mass spectrometry techniques were utilized to elucidate the structures of ten aporphine-benzylisoquinoline alkaloids, consisting of monoether link between aporphine and benzyltetrahydroisoquinoline units, which were isolated and identified previously from a variety of Thalictrum sp. (Ranunculaceae family) based mainly on the UV, IR, CD, NMR, EI-MS, CI-MS, derivatization, and chemical degradation techniques. In this investigation, protonated molecules, [M+H]+ ions, for nine tertiary alkaloids, a molecular ion, [M+'] ion, for a quaternary alkaloid, and very intense doubly- protonated molecules, [M+2H]2+ ions (100% of relative abundance) in Q1 Scan MS spectra, and prominent as well as diagnostic product ions for structural information in the tandem MS/MS spectra were observed for all investigated alkaloids each in nanogram quantities. More than 10 microg quantities of each investigated alkaloid or other isoquinoline and aporphine analogs needed for the CI-MS, EI-MS and FAB-MS analysis from the previous studies.