Straight-Phase Ion-Pair Chromatography of Zimelidine and Similar Divalent Amines Part I Bioanalysis

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Abstract
Methods for the quantitative determination of zimelidine a new antidepressant drug and its active metabolite norzimelidine in biological material (whole blood, plasma [human], urine [rat, dog and human] and rat brain) was studied. Recovery and blank chromatogram extractions were optimized and the compounds were separated by high performance ion-pair liquid chromatography with perchlorate as counter ion in the stationary phase. Internal standards were chlorpheniramine and the geometrical isomer to norzimelidine. The precision for determinations in plasma ranges 2-7% (CV (coefficient of variability)) for the concentrations 100-5 ng/ml and the detection limits was 150 pg/ml but can be lowered about 5 .times. by using larger sample volumes. The selectivity against metabolites was studied and the use of the method in routine was discussed. The isolation and identification of the primary amine metabolite by collecting the peak for subsequent GC-MS(gas chromatography-mass spectroscopy)-analysis was demonstrated.