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Pharmacokinetic study of iptacopan and its two acyl glucuronide metabolites in monkey plasma by liquid chromatography combined with electrospray ionization tandem mass spectrometry.
- Source :
-
Biomedical chromatography : BMC [Biomed Chromatogr] 2024 Nov; Vol. 38 (11), pp. e6002. Date of Electronic Publication: 2024 Sep 03. - Publication Year :
- 2024
-
Abstract
- In this study, a simple and sensitive liquid chromatography tandem mass spectrometric method was developed and validated for the determination of iptacopan and two acyl glucuronidation metabolites in monkey plasma. The plasma sample was precipitated with acetonitrile and then separated on an Acquity UPLC BEH C18 column (2.1 × 100 mm, 1.7 μm) using 0.1% formic acid and 5 mM ammonium acetate in water and acetonitrile as the mobile phase. The mass spectrometry (MS) detection was performed in positive multiple reactions monitoring (MRM) mode with precursor-to-production transitions. The developed assay was validated over the range of 1-2000 ng/mL for three analytes with correlation coefficient (r) more than 0.99. The validation parameters including accuracy, precision, carryover effect, matrix effect, recovery, and stability were all within the acceptable limits. The validated method has been applied to investigate the pharmacokinetics of iptacopan and its two acyl glucuronidation metabolites in monkey plasma. After intravenous administration, iptacopan showed low clearance (2.75 mL/min/kg) in monkey plasma. After oral administration, the bioavailability was 55.43%. The exposure (AUC <subscript>0-t</subscript> ) of direct acyl glucuronide (AG) of iptacopan accounts for 9.73% of the iptacopan plasma exposure. The AUC <subscript>0-t</subscript> of AG of dealkylated metabolite of iptacopan was present at a lower level, accounting for 0.5% of the iptacopan plasma exposure.<br /> (© 2024 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Reproducibility of Results
Male
Linear Models
Chromatography, Liquid methods
Limit of Detection
Sensitivity and Specificity
Macaca fascicularis
Benzoates
Indoles
Piperidines
Tandem Mass Spectrometry methods
Glucuronides blood
Glucuronides pharmacokinetics
Spectrometry, Mass, Electrospray Ionization methods
Subjects
Details
- Language :
- English
- ISSN :
- 1099-0801
- Volume :
- 38
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Biomedical chromatography : BMC
- Publication Type :
- Academic Journal
- Accession number :
- 39228060
- Full Text :
- https://doi.org/10.1002/bmc.6002