Sequential ortho effects: characterization of novel [M - 35](+) fragment ions in the mass spectra of 2-alkyl-4, 6-dinitrophenols.

High-resolution mass spectrometry (HRMS), hybrid tandem mass spectrometry (MS/MS) (EBqQ), and photoelectron-photoion coincidence (PEPICO) experiments were conducted to examine a possible ortho-ortho effect resulting in a novel [M - 35](+) fragment ion in 2-alkyl-4, 6-dinitrophenols. For compounds having ethyl or larger alkyl substituents, [M35](+) was observed only when [M - 18](+) ions were present, with the ortho nitro group being involved in the reaction to [M- 35](+). For [M - 18](+) and [M - 35](+), HRMS results were consistent with losses of H2O and H2O + OH, respectively, whereas MS/MS results indicated a sequential reaction due to metastable dissociations. The appearance energy determined by PEPICO for [M - 35](+) was found to be greater than the appearance energy for [M - 18](+), thus supporting a sequential reaction. 69-75).

Metabolic N-hydroxylation of pentamidine in vitro.

By using high-performance liquid chromatography, the in vitro conversion of pentamidine to the corresponding amidoximes (N-hydroxypentamidine and N,N'-dihydroxypentamidine) was studied in supernatants of rat liver homogenate centrifuged at 9,000 x g. The presence of the two amidoxime peaks in chromatograms was confirmed by liquid secondary ion mass spectrometry and by unequivocal synthesis of the suspected metabolites. The metabolic reactions were found to be catalyzed by the cytochrome P-450 system (mixed-function oxidases). The formation of the monohydroxylated product was found to have a Km of 0.48 mM and a Vmax of 29.50 pmol/min per mg of protein, while the dihydroxylated metabolite had a Km of 0.73 mM and a Vmax of 4.10 pmol/min per mg of protein. N,N'-Dihydroxypentamidine was found to have highly reduced antiprotozoal activity in vitro relative to that of pentamidine, and neither of the hydroxylated metabolites nor pentamidine was found to be significantly mutagenic by the Ames test. Contrary to previous reports, pentamidine is readily metabolized to at least two hydroxylated products, and this conversion may be relevant to the clinical use of the compound and to future drug design.

Effect of chlordecone (Kepone) on the rat brain concentration of 3-methoxy-4-hydroxyphenylglycol: evidence for a possible involvement of the norepinephrine system in chlordecone-induced tremor.

3-Methoxy-4-hydroxyphenylglycol (MHPG) is the major metabolite of norepinephrine (NE) in the rat brain. A single injection of tremorigenic doses of chlordecone to adult male Fischer-344 rats resulted in significant increases in MHPG concentrations in hypothalamus, brain stem, cerebellum, and caudate nucleus. The increase in MHPG was accompanied by a decrease in NE in the hypothalamus, suggesting that chlordecone treatment caused an increase in the turnover of NE in the brain. There was a dose- and time-related correlation between the increases in the concentrations of MHPG in hypothalamus, brain stem, and cerebellum and tremor in rats. The increase in MHPG in hypothalamus and brain stem occurred as early as 1 hr postdosing; this preceded the earliest measurable sign of tremor and initial hypothermia. Whether the alterations in the brain NE system are involved in the expression of the tremor and the initial hypothermia induced by chlordecone or whether they are merely associated with these changes is not clear.

Fractionation of alkali metal cations in cationization of phthalic acid. A fast atom bombardment study.

Competition for solvent glycerol and solute phthalic acid by the alkali metal cations Li+, Na+, K+, Rb+ and Cs+ in cationization fast atom bombardment spectra is quantitated.