Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
High-performance liquid chromatographic determination of a potent and selective HIV protease inhibitor (L-735,524) in rat, dog and monkey plasma.
J Chromatogr B Biomed Appl. 1995 Oct 6;672(1):111-7. Unique Identifier : AIDSLINE MED/96128899 Chen IW; Vastag KJ; Lin JH; Department of Drug Metabolism I, Merck Research Laboratories,; West Point, PA 19486, USA.
Abstract:
A high-performance liquid chromatographic method coupled with liquid-liquid sample extraction and ultraviolet detection has been developed for the quantification of L-735,524 (I), a potent, highly selective and orally bioavailable inhibitor of recombinant human immunodeficiency virus (HIV) protease in rat, dog and monkey plasma. The present method is reproducible and reliable with limits of quantification of 25, 12.5 and 6.25 ng/ml, respectively for rat, dog and monkey plasma. The standard curve was linear over the range of 6.25-2000 ng/ml in the biological fluid. The mean coefficients of variation for concentration within the range of standard curve were 7.94, 6.91 and 4.52%, respectively, for intra-day analysis and 5.58, 9.27 and 5.45%, respectively, for inter-day analysis. The recoveries of I and L-707,943 (II), an analog of I used as the internal standard, from plasma samples were all over 88% through the extraction procedure. I and II are stable in mobile phase over a 48-h period while waiting for injection at ambient temperature and over a 144-h period in rat, dog and monkey plasma while stored at -20 degrees C. Aqueous solubility of I is pH dependent, 60 mg/ml at pH 3.5 and 0.3 mg/ml at pH 4.8. The analytic procedures described in this report have been successfully employed to quantify the concentration of I in rat, dog and monkey plasma and provide the kinetic information for toxicological and pharmacological studies.
Keywords: Administration, Oral Animal *Chromatography, High Pressure Liquid Comparative Study Dogs Human Hydrogen-Ion Concentration HIV Protease Inhibitors/ADMINISTRATION & DOSAGE/*BLOOD/CHEMISTRY/ PHARMACOKINETICS Injections, Intravenous Intestinal Absorption Macaca mulatta Male Pyridines/ADMINISTRATION & DOSAGE/*BLOOD/CHEMISTRY/ PHARMACOKINETICS Rats Rats, Sprague-Dawley Solubility Solutions Spectrophotometry, Ultraviolet JOURNAL ARTICLE
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Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.
