Determination of denzimol, a new anticonvulsant agent, and its main metabolite in biological material by gas chromatography and high-performance liquid chromatography.
Two methods, using gas chromatography (GC) and high-performance liquid chromatography (HPLC), were developed in order to investigate the pharmacokinetics of denzimol hydrochloride, N-[beta-[4-(beta-phenylethyl)phenyl]-beta-hydroxyethyl] imidazole hydrochloride, which is a new anticonvulsant drug, and of its main metabolite, N-[beta-[4-(beta-phenyl-beta(alpha)-hydroxyethyl)phenyl] -beta-hydroxyethyl]-imidazole (referred to as M2), in humans. Both methods involve the use of a homologue of denzimol as an internal standard. The GC method is more sensitive (sensitivity limit 2.5 ng/ml for denzimol and 15 ng/ml for M2) and was utilized for the determination of denzimol and M2 in plasma. The GC method is specific, precise (relative standard deviations are 3.26, 2.12 and 1.72% at 10, 100 and 1000 ng/ml for denzimol and 6.45, 4.17 and 3.38% at 50, 500 and 1000 ng/ml for M2) and accurate (mean recovery +/- S.D. is 102.58 +/- 4.10% for denzimol and 99.72 +/- 7.75% for M2). The HPLC method is very simple and quick to perform. This method has a sensitivity limit of 0.5 micrograms/ml for denzimol and 1 microgram/ml for M2, and allows the determination of both compounds in urine with high selectivity, reproducibility (relative standard deviations are 2.05, 3.50 and 1.02% for denzimol and 2.78, 2.80 and 1.73% for M2, at concentrations of 15, 35 and 70 micrograms/ml) and accuracy (mean recovery +/- S.D. is 103.57 +/- 2.97% for denzimol and 95.91 +/- 1.59% for M2). The common anticonvulsants, when present in plasma, do not interfere with the monitoring of denzimol levels.
D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood / Q000652:urine; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000032:analysis* / Q000097:blood / Q000652:urine; D007202:Indicators and Reagents; D013056:Spectrophotometry, Ultraviolet
D000927:Anticonvulsants; D007093:Imidazoles; D007202:Indicators and Reagents; C031307:denzimol