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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Identification and quantitation of 1-arylpiperazines, metabolites resulting from side-chain cleavage of (4-substituted aryl-1-piperazinyl)alkyl heterocyclic derivatives in rat plasma and brain.

Many drugs contain the arylpiperazine moiety in the side-chain of their molecules. A common metabolic pathway of such drugs is cleavage of the side-chain with the formation of 1-arylpiperazines. This has been verified by combined gas chromatography-mass spectrometry of biological samples from rats given orally a series of heterocyclic derivatives bearing a 4-aryl(phenyl, pyrimidinyl, pyridyl or thiazolyl)-1-piperazinylalkyl moiety (oxypertine, zolertine, millipertine, empiprazole, dapiprazole, antrafenine, piribedil, azaperone). A sensitive and selective electron-capture gas-liquid chromatographic procedure for 1-arylpiperazines in rat plasma and brain is described. The overall recovery from plasma and brain was 70-90%. The limit of detection for substituted (halogenated) phenylpiperazines was 10-25 ng/ml or ng/g and 25-100 ng/ml or ng/g for other derivatives. Preliminary data are reported on the time course of the production and elimination of 1-arylpiperazines after oral administration of representative compounds with the arylpiperazine moiety (oxypertine, azaperone and S-3608).[1]


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