Plasma Analysis of Benazepril Using Gas Chromatography with Mass-Selective Detection GC-MSD

The NPD is a destructive detector that can be used in series only after non-destructive detectors (e.g. ECD). The NPD is sensitive to water that affects the condition of the thermoionic bead. The active element of the bead eventually will become depleted (especially when using halogenated solvents like dichloromethane, chloroform etc.) and requires replacement. 

Due to the discovery of two further urinary metabolites of ramipril (the respective diketopiperazine derivatives of ramipril and ramiprilat), the above-described method was slightly modified (Schmidt et al. 1985). Instead of the rather time consuming second extraction step by means of a disposable Si column, the sample is cleaned by a liquid/liquid extraction step. After methylation of the compounds with diazomethane, the eluate is evaporated to dryness at 40 °C under N2 gas. Subsequently the residue is dissolved in n-pentane/diethyl ether (3 2. v/v) and washed with 5% hydrogen carbonate solution. After separation of the upper organic layer, this is evaporated to dryness at 40 °C under N2 gas and then treated with 1 mL n-hexane/TFAA (5%) as described before (Hajdu et al. 1984). This method allows the selective determination of ramipril and its three metabolites in human urine the limit of quantification amounted to 0.020 xg/mL for each of all four analytes. Using this assay, thousands of urine samples originating from phase I—III clinical studies were analysed. 

In the following assay, the application of capillary gas chromatography for the determination of another ACE inhibitor, but this time in human plasma and with mass selective detection, is described. 

Albro PW, Fishbein L (1969) Determination of prostaglandins by gas-liquid chromatography. J of Chromatogr 

Hajdu P, Schmidt D, Bomm M, Keller A (1984) Determination of (2-[N-[(S)-l-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S,5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid) (HOE 498) and its hydrolysis product in serum and urine. Arznm Forsch/Drug Res 34 1431-1435 Schmidt D, Keller A (1985) Sensitive determination of the ACE-Inhibitor HOE 498 and its metabolites in human urine by capillary GC. Fresenius Z Anal Chem 320 731 Walle T, Ehrsson H, Bogentoft C, Dolby J (1972) Synthesis and structure of an enaminic bis(trifluoroacetyl) derivatives of desipramine. Acta Pharm Suecica 9 509-512 

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II.Q.2 Plasma Analysis of Benazepril Using Gas Chromatography with Mass-Selective Detection (GC-MSD) 633... 

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