Detection and time course of cocaine N-oxide and other cocaine metabolites in human plasma by liquid chromatography/tandem mass spectrometry

Gas chromatography/mass spectrometry (GC/MS) is often used for detection and measurement of cocaine metabolites in biological specimens. However, cocaine N-oxide, a recently identified metabolite of cocaine, is thermally degraded when introduced into a GC/MS. The major degradation products are cocaine and norcocaine. When cocaine N-oxide was measured in rat plasma using liquid chromatography in combination with electrospray ionization-mass spectrometry (LC/ESI-MS), the cocaine N-oxide concentrations in the rat plasma were reported to be as high as 30% of the cocaine concentrations. However, in our study involving LC/ESI-MS/MS analysis of plasma collected from human subjects following administration of oral cocaine, we determined that the concentrations of cocaine N-oxide relative to the cocaine concentrations never exceeded 3%. This suggests that determination of cocaine concentration in human plasma by GC/MS analysis will not significantly distort the actual cocaine concentrations due to thermal conversion of cocaine N-oxide to cocaine. In the work reported here, we compared results obtained using GC/MS, LC/ESI-MS/MS, and liquid chromatography/atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) to determine thermal degradation of cocaine N-oxide. LC/ ESI-MS/MS was selected to determine cocaine, benzoylecgonine, and cocaine N-oxide, and LC/APCI-MS/MS was selected to determine ecgonine methyl ester and norcocaine in plasma collected from three human subjects participating in a clinical study. The resulting time course data provide additional information into kinetic interrelationships between cocaine N-oxidation and cocaine hydrolysis.     

Fe2O3-Modified Porous BiVO4 Nanoplates with Enhanced Photocatalytic Activity

Nano-Micro Letters - As BiVO4 is one of the most popular visible-light-responding photocatalysts, it has been widely used for visible-light-driven water splitting and environmental purification....     

The mechanical properties of rubber-modified vinyl esters

“Vinyl esters” were prepared by reacting an epoxy resin (DGEBA) with acrylic and methacrylic acids, modified with Hycar VTBN, and cured at 90°C for 4 h with t-butyl perbenzoate. The resultant materials showed a two-phase structure in electron micrographs and dynamic mechanical spectra. The domain of the dispersed phase was estimated to be on the order of 10 nm in size. Infrared spectroscopy indicated extensive copolymerization of the internal double bonds or pendant vinyl groups in VTBN during the cure of the resin. The mechanical properties of the modified materials were measured, and the differences in mechanical behavior between the acrylic and methacrylic vinyl esters were discussed.     

Repeated dosing with oral cocaine in humans: Assessment of direct effects, withdrawal, and pharmacokinetics.

Cocaine withdrawal symptoms are thought to play a role in relapse; studies characterizing the symptomatology have yielded mixed findings. This study sought to examine the pharmacodynamic/pharmacokinetic profile of repeated high dose exposure to oral cocaine and characterize acute and protracted withdrawal in cocaine abusers. This study employed a repeated-dosing, single-blind design in which subjects (n = 9), resided for 40 days on a closed ward. They were maintained for two 4-day cocaine exposure periods (Days 1–4 & Days 9–12, cocaine 175 mg, p.o.; 5 hourly doses; 875 mg/day) separated by a 4-day matched placebo exposure period (Days 5–8). After these 12 days, an additional period of 28 days of placebo maintenance followed (Days 13–40). Test sessions were conducted during each phase; measures of mood, drug effects, sleep, pharmacokinetics, and prolactin were collected throughout the study. The dosing regimen produced cocaine plasma concentrations (Cmax of 680 ng/mL) two to threefold higher than typically seen in acute dose studies. Prototypic psychostimulant effects, including subjective ratings of euphoric effects (liking, high, good effects) and significant cardiopressor effects, were sustained during the active dosing periods, corresponding to the rise and fall of plasma cocaine. Withdrawal-like symptoms (i.e., disruptions of sleep, increased ratings of anxiety, irritability, crashing) were observed within 24-hr after cessation of dosing. Cocaine reduced prolactin acutely, but no sustained alterations were observed for this measure or for other signs or symptoms during the 28-day abstinence period. These findings indicate that exposure to controlled high doses of cocaine produces modest symptoms consistent with cocaine withdrawal within hours of cessation of dosing but provide no evidence of symptoms persisting beyond 24 hours. (PsycINFO Database Record (c) 2010 APA, all rights reserved)