Electron capture plasma studies

Clinical investigations of A -tetrahydrocannabinol (4,5) and ll-hydroxy-A -tetrahydrocannabinol (6) have relied upon analysis by radioactive labeling. However, the study of distribution, metabolism and excretion of the drug and its metabolites under chronic or "street" conditions demands nonradioactive analytical procedures. When plasma suspensions of l c-A -tetrahydrocan-nabinol were administered intravenously to three dogs at doses of 0.1 - 2.0 mg/kg and plasma levels of 1 were followed for up to 7000 minutes, no significant differences were seen in 1 plasma levels as determined by liquid scintillation and electron capture detection (GLC) after HPLC collection. 

The recovery of 1 from the heptane extract of dog plasma by normal phase HPLC was reproducible over the range of plasma concentrations studied. Equivalent overall recoveries were obtained by both radiochemical analysis (83.7 1.8% SE) and electron-capture GLC analysis (84.0 4.9% SE) of the derivatized tetrahydrocannabinol. ... 

The external factors influencing nimodipine concentrations during intravenous administration were studied using GC-electron-capture detection [18]. Nimodipine was extracted from plasma and analyzed using a column (1.8 m x 2 mm) packed with 3% of OV-17 on gas-Chrom Q (50-100 mesh). The column was operated at 255°C with nitrogen as the carrier gas (flow rate of 25 mL/min), and 63 Ni ECD. The calibration graph was linear for upto 1000 ng/mL, and the limit of detection was 0.5 ng/mL. 

Wotiz and Chattoraj (Wll) studied the specificity, accuracy, sensitivity, adaptability, and the sources of error in the analysis of estrogens using thin-layer and gas-liquid chromatography. Their method permits the determination of as little as 0.2 j g of estrogen per 24 hours. Free estrone in blood plasma has been determined by Attal, Hendeles, and Eik-Nes (AlO) using GLC with electron-capture detection. GLC was used by Ruchelman (R3) in solubility studies of estrone in organic solvents. 

Studies of gaseous electron capture taking place in a plasma were reported by Wentworth et al. (18). The equilibrium established in a plasma between e, A, and A " allowed the determination of the absolute electron affinities of the aromatic hydrocarbons in the gas phase. 

Karasek, F.W. Tatone, O.S. Kane, D.M., Study of electron capture behavior of substituted aromatics by plasma chromatography, Anal. Chem. 1973,45,1210-1214. 

Determination of Desmethyldiazepam in Plasma by Electron-Capture GLC Application to Pharmacokinetic Studies of Clorazepam J. Pharm. Sci. 67(3) 427-429 (1978) ... 

Further Studies on the Gas-Liquid Chromatographic Determination of C19-Steroids in Human Plasma Using Nickel-63 Electron Capture Detection... 

Rapid Determination of Diazepam and Nordiazepam in Plasma by Electron Capture Gas-Liquid Chromatography. Application in Clinical Pharmacokinetic Studies... 

Example 4-Hydroxynon-2-enal (4-HNE) is a major aldehydic product of lipid peroxidation (LPO), its products being indicators for oxidative stress. In order to introduce LPO products as biomarkers, a GC-MS method for 4-HNE detection in clinical studies [35] was developed using a sample volume of 50 pi of plasma. For improved GC separation and subsequent mass spectral detection the aldehyde is converted into the pentafluorobenzyl-hydroxylimine and the hydroxy group is tri-methylsilylated [36]. The TIC acquired in electron capture mode (EC, Chap. 7.4) exhibits 50 chromatographic peaks (Fig. 14.2). Those related to the target compounds can easily be identified from suitable RICs. The choice of potentially useful m/z values for RICs is made from the EC mass spectrum of the pure 4-HNE derivative (below). In this case, [M-HF], m/z 403, [M-HOSiMes] , m/z 333, and [CeFs]", m/z 167, are indicative, while [CH2C6F5] , m/z 181, is not. 

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