Quantitative analytical methods for the determination of a new hypertension drug, CGS 25462, and its metabolites (CGS 25659 and CGS 24592) in human plasma by high-performance liquid chromatography.

Abstract

Two simple and sensitive reversed-phase high-performance liquid chromatography (HPLC) methods were developed and validated for the quantitative determination of a novel hypertension drug CGS 25462 and its major metabolites CGS 24592 and CGS 25659 in human plasma. CGS 25462 and CGS 25798 (internal standard) were purified by one-step liquid-liquid extraction with methylene chloride. The metabolites were analyzed on HPLC after plasma protein precipitation with 10% trichloroacetic acid (TCA). Separations were achieved on a Zorbax RX C18 column. All compounds were detected by using a fluorescence detector. The excitation wavelength was 254 nm, and emission was monitored at 325+/-12.5 nm. Assessment of recovery and reproducibility indicated good accuracy and precision. Over the validation concentration range of 10 to 1000 ng/ml for CGS 25462 and 25 to 5000 ng/ml for both metabolites, overall mean relative recoveries were 96% for CGS 25462, 101% for CGS 25659 and 107% for CGS 24592, and the coefficients of variation were 4.6 to 13% for CGS 25462, 9.5 to 13% for CGS 25659 and 7.7 to 15% for CGS 24592. The limits of quantification (LOQs) were 10 ng/ml for CGS 25462 and 25 ng/ml for CGS 24592 and CGS 25659, which were of sufficient sensitivity to measure the concentrations of CGS 25462, CGS 25659 and CGS 24592 in plasma samples from normal volunteers following a single 800 mg oral dose.

• Authors: W M Maniara, A Cipriano, M L Powell
• Journal: Journal of chromatography. B, Biomedical sciences and applications (J Chromatogr B Biomed Sci Appl) Vol. 706 Issue 2 Pg. 287-94 (Mar 20 1998) ISSN: 1387-2273 [Print] Netherlands
• PMID: 9551815 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antihypertensive Agents
• Biphenyl Compounds
• CGS 24592
• CGS 25659
• Organophosphonates
• Prodrugs
• Protease Inhibitors
• CGS 25462
• Phenylalanine

Topics

• Administration, Oral
• Antihypertensive Agents (administration & dosage, blood, chemistry, pharmacokinetics)
• Biphenyl Compounds (administration & dosage, blood, chemistry, pharmacokinetics)
• Chromatography, High Pressure Liquid (methods)
• Circadian Rhythm
• Half-Life
• Humans
• Male
• Organophosphonates (administration & dosage, blood, chemistry, pharmacokinetics)
• Phenylalanine (analogs & derivatives, blood, chemistry)
• Prodrugs (administration & dosage, chemistry, pharmacokinetics)
• Protease Inhibitors (administration & dosage, blood, chemistry, pharmacokinetics)
• Reproducibility of Results
• Sensitivity and Specificity
• Temperature
• Time Factors