Comparative bioanalytical study of³H-deramciclane in dog plasma, using a gas chromatography-nitrogen-selective detection (GC-NPD), a new GC-radiochemical detection (GC-RD) and a liquid scintillation method

Summary

A new, highly sensitive and selective gas chromatography method, using radiochemical detection (GC-DR) was developed for the selective determination of³H-labelled deramciclane and its N-desmethyl metabolite in dog plasma. Inter-day accuracy and precision, as well as system suitability of the GC-RD method was investigated during the method validation. The calibration curve was proved to be linear (r=0.9986) in a wide concentration range (13–1000 ngeqv mL⁻¹)

The lower limit of quantitation (LLOQ) was 13.7 ngeqv mL⁻¹, and the limit of the detection (LOD) was 1 ngeqv mL⁻¹.

Using this new GC-RD method, plasma levels of³H-labelled deramciclane and its metabolite were determined in dogs, after the administration of a single 10 mg kg⁻¹ oral dose. Pharmacokinetic curves and the calculated pharmacokinetic parameters were compared to those obtained using a previously elaborated gas chromatography-nitrogen selective detection method (GC-NPD) and to those obtained by measuring the plasma level of total radioactivity (liquid scintillation counting, LSC). Pharmacokinetic curves and the calculated pharmacokinetic parameters obtained with the two different gas chromatography detection methods (NPD and RD) showed good correlation. Comparison of these results to those acquired by total radioactivity measurement demonstrated that deramciclane was intensively metabolised. Moreover, the biological half-life (t ^2/β₁ ) of the unknown metabolites proved to be more than a magnitude longer than the half-life of the parent compound or that of N-desmethyl metabolite.