RESUMO
Extraction of DMP 450 from plasma was performed with C2 solid-phase extraction columns, using 0.1 M ammonium acetate in 90% methanol to elute DMP 450. The extraction recovery over the range of 10 to 10 000 ng/ml averaged 81.0, 96.2, 77.4, 95.2 and 68.0% from rat, dog, monkey, chimpanzee (25-10 000 ng/ml) and human plasma, respectively. HPLC analysis was carried out with a C18 column and a mobile phase of acetonitrile, methanol and 30 mM potassium phosphate (pH 3), the composition dependent on the type of plasma being analyzed, and monitored at a wavelength of 229 nm. Intra-day and inter-day coefficients of variation were less than 9.9 and 12.9%, respectively. Absolute differences were less than 11.5%.
Assuntos
Azepinas/sangue , Cromatografia Líquida de Alta Pressão/métodos , Inibidores da Protease de HIV/sangue , Ureia/análogos & derivados , Acetonitrilas , Animais , Cromatografia Líquida de Alta Pressão/estatística & dados numéricos , Cães , Haplorrinos , Humanos , Concentração de Íons de Hidrogênio , Metanol , Pan troglodytes , Fosfatos , Compostos de Potássio , Ratos , Sensibilidade e Especificidade , Ureia/sangueRESUMO
A sensitive and selective high-performance liquid chromatographic method for the determination of XR510 (I), a new non-peptide angiotensin II (AII) receptor antagonist with balanced affinity for AT1 and AT2 receptor subtypes is described. I and the internal standard, XR513, were extracted from acidified plasma by combined liquid-liquid/solid-phase extraction and chromatographed on a phenyl column with ultraviolet absorbance detection at a wavelength of 272 nm. The mobile phase consisted of a mixture of acetonitrile and sodium phosphate buffer. For both rat and dog plasma, the limit of quantitation was 5 ng/ml. This method has been validated and successfully utilized to investigate the disposition of I.