Determination of plasma and brain concentrations of trazodone and its metabolite, 1-m-chlorophenylpiperazine, by gas-liquid chromatography

Abstract

A sensitive and specific gas chromatographic procedure is described for the quantitation of trazodone and its active metabolite, 1-m-chlorophenylpiperazine (mCPP), in plasma and brain. After addition of internal standards, the samples were extracted with benzene and the extracts divided into two portions. One portion was evaporated to dryness, and residue dissolved in methanol and the solution injected into a gas chromatograph equipped with a nitrogen-selective detector, for trazodone quantitation. To the remaining half of the extracts, 100 microliter of heptafluorobutyric anhydride solution were added and the metabolite was measured as the heptafluorobutyryl derivative by electron-capture detection. Gas chromatography-mass spectrometry was used to confirm the specificity of the analyses. The kinetic profile of trazodone and its metabolite was investigated after oral administration of trazodone (25 mg/kg). The parent drug and its metabolite both accumulated in brain, reaching concentrations several times those in plasma. More mCPP than the parent compound entered the brain; the ratio of the area under the curve for trazodone to mCPP in plasma was about 4, whereas in brain it was only about 0.8.