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Measurement of bempedoic acid and its keto metabolite in human plasma and urine using solid phase extraction and electrospray LC-MS/MS.
- Source :
-
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences [J Chromatogr B Analyt Technol Biomed Life Sci] 2020 Oct 01; Vol. 1154, pp. 122291. Date of Electronic Publication: 2020 Jul 30. - Publication Year :
- 2020
-
Abstract
- Bempedoic acid, a new therapeutic for treatment of hypercholesterolemia, inhibits hepatic ATP-citrate lyase in the cholesterol synthesis pathway after its conjugation with coenzyme A. Sensitive and selective methods were required to study the pharmacokinetic behavior of bempedoic acid and its active 8-keto metabolite in clinical studies. A mixed mode anion exchange extraction on 96-well plates was developed to favor high, selective recoveries of these dicarboxylic acids from urine or plasma. Adsorptive losses in urine led to inaccurate measurements unless samples were acidified and diluted with isopropanol prior to any specimen transfers. Tandem mass spectrometry with negative ion electrospray ionization permitted lower limits of measurement of 20 and 10 ng/mL for the drug and metabolite in either matrix. The methods were validated to current regulatory standards and have been the basis for pharmacokinetic measurements in 26 clinical studies involving over 15,000 samples.<br />Competing Interests: Declaration of Competing Interest Esperion Therapeutics, Inc. as the sponsor outsourced method development and validation to AIT Bioscience, for which BE, RS, KP, and CB are employees. CTC is a shareholder in Esperion Therapeutics.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Humans
Linear Models
Reproducibility of Results
Sensitivity and Specificity
Chromatography, Liquid methods
Dicarboxylic Acids blood
Dicarboxylic Acids isolation & purification
Dicarboxylic Acids metabolism
Dicarboxylic Acids urine
Fatty Acids blood
Fatty Acids isolation & purification
Fatty Acids metabolism
Fatty Acids urine
Solid Phase Extraction methods
Tandem Mass Spectrometry methods
Subjects
Details
- Language :
- English
- ISSN :
- 1873-376X
- Volume :
- 1154
- Database :
- MEDLINE
- Journal :
- Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
- Publication Type :
- Academic Journal
- Accession number :
- 32763847
- Full Text :
- https://doi.org/10.1016/j.jchromb.2020.122291