A gas chromatographic mass spectrometric assay has been developed for the determination of cocaine and its pharmacologically active metabolite, norcocaine, in human urine. [2H3]Cocaine and [2H3]norcocaine were used as internal standards. The assay utilizes selective focusing to monitor in a gas chromatographic effluent the molecular ions of cocaine, [2H3]cocaine and the fragment ions of trifluoroacetylated norcocaine, [2H3]norcocaine generated by electron impact ionization. The assay can measure 2 ng ml-1 each of cocaine and norcocaine with about 5% precision. The curves, relating the amounts of cocaine and norcocaine added to control urine per 'fixed' amounts of their labeled analogs, versus the appropriate ion intensity ratios are straight lines with nearly zero intercepts and slopes of 0.98 +/- 0.01 and 0.98 +/- 0.02, respectively. The methodology is used for the analysis of urinary cocaine and norcocaine from three human subjects who received 100 mg cocaine-HCL intravenously.
Deuterium exchange of bicyclic ketones in 2:1 (v/v) dioxane-D20 catalyzed by NaOD was measured by a mass spectrometric technique developed for this purpose. Second-order rate constants (M-1 sec-1) at 25.0°a nd activation parameters AH* (kcal mol-1) and AS* (eu) were determined as follows: bicyclo[2.2.2]octan-2-one (1) 3.03 X 10-2, 13.1, and -21; bicyclo[2.2.1]heptan-2-one (2) 5.58 X 10-2, 14.0, and -17 (exo); 8.26 X 10-6, 17.1, and -20 (endo); and bicyclo[2.1.1]hexan-2-one (3) 6.04 X 10-6, 17.8 and -23. The rate of base-catalyzed bromination of cyclohexanone was found to exceed that of 1 by a factor of 3.1 in water at 10.0°. The secondary isotope effect £d/&h for deuteration of 1 was 0.94 ± 0.04 at 25.0°. These results are interpreted as showing that the rates reflect the relative facility of proton abstraction from the different sites, and that the principal factors governing the rates of attack are the angle strain generated in the resulting enolates, which favors reactivity in the series 1 > 2 > 3, and the greater steric blocking of access of the base to the reaction site by a two-carbon bridge as opposed to a one-carbon bridge, which favors reactivity in the series exo-2 > endo-2, and 3 > 1. Bicyclic ring systems have been widely used as substrates for the examination of organic reactions, particularly the steric requirements of those reac-(1) Address correspondence concerning this work to the University of Toronto. For part III, see ref 2a. Portions of this work were reported in preliminary communications, ref 2b,c.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.