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Stereoselective determination of propranolol enantiomer in transgenic cell lines expressing human cytochrome P450 / 浙江大学学报·医学版
Journal of Zhejiang University. Medical sciences ; (6): 116-120, 2003.
Artículo en Chino | WPRIM | ID: wpr-231106
ABSTRACT
<p><b>OBJECTIVE</b>To establish a chiro chromatography for studying the stereoselective metabolism of propranolol (PL) in S(9) incubates prepared from transgenic cell lines expressing human cytochrome P450.</p><p><b>METHODS</b>The concentration of each enantiomer in S(9) incubates was determined through precolumn derivatization with GITC, followed by RP-HPLC assay using S-(+)-propafenone as internal standard.</p><p><b>RESULTS</b>Baseline separations among the diastereomers of S(-)-P, internal standard and R(+)-PL were achieved on Shimpack CLC C(18)ODS column, with UV detection and methanolwaterglacial acetic acid (67/33/0.05,v/v/v) as mobile phase. The assay was simple, accurate, precise and specific. The linear range was from 5 to 500 micromol/L for each enantiomer. The limit of quantitation (LOQ) for the method was 5 micromol/L for the S(-)-and R(+)-PL, respectively (n=5, RSD<10%). The analytical method afforded average recoveries of 98.7 and 98.1% for S(-)- and R(+)-PL, respectively. The reproducibility of the assay was good (RSD<10%). The time-dependent studies showed that PL had the stereoselectivity of S-(-)-isomer in metabolism via CYP2C18 and the stereoselectivity of R-(+)-isomer in metabolism via CYP2C9.</p><p><b>CONCLUSION</b>The method allows to study of stereoselective metabolism of PL in vitro.</p>
Asunto(s)
Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fisiología / Propranolol / Estereoisomerismo / Reproducibilidad de los Resultados / Cromatografía Líquida de Alta Presión / Transgenes / Sistema Enzimático del Citocromo P-450 / Genética / Metabolismo Límite: Humanos Idioma: Chino Revista: Journal of Zhejiang University. Medical sciences Año: 2003 Tipo del documento: Artículo

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Texto completo: Disponible Índice: WPRIM (Pacífico Occidental) Asunto principal: Fisiología / Propranolol / Estereoisomerismo / Reproducibilidad de los Resultados / Cromatografía Líquida de Alta Presión / Transgenes / Sistema Enzimático del Citocromo P-450 / Genética / Metabolismo Límite: Humanos Idioma: Chino Revista: Journal of Zhejiang University. Medical sciences Año: 2003 Tipo del documento: Artículo