Comparative bioanalytical study of H-3-deramciclane in dog plasma, using agas chromatography nitrogen-selective detection (GC-NPD), a new GC-radiochemical detection (GC-RD) and a liquid scintillation method
J. Szunyog et al., Comparative bioanalytical study of H-3-deramciclane in dog plasma, using agas chromatography nitrogen-selective detection (GC-NPD), a new GC-radiochemical detection (GC-RD) and a liquid scintillation method, CHROMATOGR, 48(1-2), 1998, pp. 133-139
A new, highly sensitive and selective gas chromatography method, using radi
ochemical detection (GC-RD) was developed for the selective determination o
f H-3-labelled deramciclane and its N-desmethyl metabolite in dog plasma. I
nter-day accuracy and precision, as well as system suitability of the GC-RD
method was investigated during the method validation. The calibration curv
e was proved to be linear (r = 0.9986) in a wide concentration range (13-10
00 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 of H-3-labelled deramciclane and
its metabolite were determined in dogs, after the administration of a sing
le 10 mg kg(-1) oral dose. Pharmacokinetic curves and the calculated pharma
cokinetic parameters were compared to those obtained using a previously ela
borated gas chromatography-nitrogen selective detection method (GC-NPD) and
to those obtained by measuring the plasma level of total radioactivity (li
quid scintillation counting, LSC). Pharmacokinetic curves and the calculate
d pharmacokinetic parameters obtained with the two different gas chromatogr
aphy detection methods (NPD and RD) showed good correlation. Comparison of
these results to those acquired by total radioactivity measurement demonstr
ated that deramciclane was intensively metabolised. Moreover, the biologica
l half-life (t(1/2)(beta)) of the unknown metabolites proved to be more tha
n a magnitude longer than the half-life of the parent compound or that of N
-desmethyl metabolite.