Determination of XR510, a balanced angiotensin II receptor antagonist, in dog and rat plasma by combined liquid-liquid/solid-phase extraction and high-performance liquid chromatography.
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.
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Drug Metabolism and Pharmacokinetics, DuPont Merck Pharmaceutical Company, Newark, DE 19714, USA.
Krauthauser
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Huang
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D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D007093:Imidazoles / Q000097:blood*; D051381:Rats; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; C095055:XR 510