Back to Search
Start Over
Overcoming bioanalytical challenges associated with the separation and quantitation of GSK1278863, a HIF-prolyl hydroxylase inhibitor, and its 14 stereoisomeric metabolites
- Source :
- Journal of Chromatography B. :7-16
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
Abstract
- GSK1278863 is an investigative drug under investigation for treatment of anemia associated with chronic kidney disease. Its metabolism is primarily metabolized by P450 enzymes where 19 unique metabolic species have been identified. These include multiple products of mono-, di-, and tri-oxygenation. Initially, two separate and complex ultra high performance liquid chromatography (UHPLC) reverse phase methodologies were developed, validated and applied to measure parent and various predominant and circulating metabolites in numerous clinical studies. However, 5 of the 6 oxidative metabolites may exist in different stereoisomeric forms, resulting in 14 separate species; therefore a chiral methodology was required to determine which stereoisomeric forms circulated in human. A variety of conventional approaches were explored, where in the end a supercritical fluid chromatography (SFC) method was required to separate this complex mixture of 14 stereoisomeric metabolites; data from these experiments provided important information on which species circulate in human. The details of these methodologies will be discussed herein.
- Subjects :
- Bioanalysis
Clinical Biochemistry
Glycine
Stereoisomerism
030226 pharmacology & pharmacy
01 natural sciences
Biochemistry
Analytical Chemistry
03 medical and health sciences
0302 clinical medicine
Cytochrome P-450 Enzyme System
Humans
P450 Enzymes
Chromatography, High Pressure Liquid
Chromatography, Reverse-Phase
Chromatography
Chemistry
010401 analytical chemistry
Reproducibility of Results
Chromatography, Supercritical Fluid
Prolyl-Hydroxylase Inhibitors
Oxidation reduction
Cell Biology
General Medicine
HIF prolyl-hydroxylase inhibitor
Metabolism
0104 chemical sciences
Barbiturates
Supercritical fluid chromatography
Ultra high performance
Oxidation-Reduction
Subjects
Details
- ISSN :
- 15700232
- Database :
- OpenAIRE
- Journal :
- Journal of Chromatography B
- Accession number :
- edsair.doi.dedup.....872443b10c356d1957d3940e847ccc79