Data/hora: 04/06/2024 04:45:33

Provedor de dados: 	Brazilian Journal of Medical and Biological Research	
País: 	Brazil	
Título: 	A micromethod for quantitation of debrisoquine and 4-hydroxydebrisoquine in urine by liquid chromatography	
Autores: 	Pereira,V.A.; Auler Jr.,J.O.; Carmona,M.J.; Mateus,F.H.; Lanchote,V.L.; Breimer,D.D.; Santos,S.R.C.J.	
Data: 	2000-05-01	
Ano: 	2000	
Palavras-chave: 	Debrisoquine; 4-hydroxydebrisoquine; HPLC-F; Urinary excretion kinetics; Debrisoquine test validation; CYP2D6.	
Resumo: 	We describe a new simple, selective and sensitive micromethod based on HPLC and fluorescence detection to measure debrisoquine (D) and 4-hydroxydebrisoquine (4-OHD) in urine for the investigation of xenobiotic metabolism by debrisoquine hydroxylase (CYP2D6). Four hundred µl of urine was required for the analysis of D and 4-OHD. Peaks were eluted at 8.3 min (4-OHD), 14.0 min (D) and 16.6 min for the internal standard, metoprolol (20 µg/ml). The 5-µm CN-reverse-phase column (Shimpack, 250 x 4.6 mm) was eluted with a mobile phase consisting of 0.25 M acetate buffer, pH 5.0, and acetonitrile (9:1, v/v) at 0.7 ml/min with detection at lexcitation = 210 nm and lemission = 290 nm. The method, validated on the basis of measurements of spiked urine, presented 3 ng/ml (D) and 6 ng/ml (4-OHD) sensitivity, 390-6240 ng/ml (D) and 750-12000 ng/ml (4-OHD) linearity, and 5.7/8.2% (D) and 5.3/8.2% (4-OHD) intra/interassay precision. The method was validated using urine of a healthy Caucasian volunteer who received one 10-mg tablet of Declinax®, po, in the morning after an overnight fast. Urine samples (diuresis of 4 or 6 h) were collected from zero to 24 h. The urinary excretion of D and 4-OHD, Fel (0-24 h), i.e., fraction of dose administered and excreted into urine, was 6.4% and 31.9%, respectively. The hydroxylation capacity index reported as metabolic ratio was 0.18 (D/4-OHD) for the person investigated and can be compared to reference limits of &amp;gt;12.5 for poor metabolizers (PM) and &amp;lt;12.5 for extensive metabolizers (EM). In parallel, the recovery ratio (RR), another hydroxylation capacity index, was 0.85 (4-OHD: SD + 4-OHD) versus reference limits of RR &amp;lt;0.12 for PM and RR &amp;gt;0.12 for EM. The healthy volunteer was considered to be an extensive metabolizer on the basis of the debrisoquine test.	
Tipo: 	Info:eu-repo/semantics/other	
Idioma: 	Inglês	
Identificador: 	http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2000000500004	
Editor: 	Associação Brasileira de Divulgação Científica	
Relação: 	10.1590/S0100-879X2000000500004	
Formato: 	text/html	
Fonte: 	Brazilian Journal of Medical and Biological Research  v.33 n.5 2000	
Fonte: 	info:eu-repo/semantics/openAccess