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Determination of Novel Highly Effective Necrostatin Nec-1s in Rat Plasma by High Performance Liquid Chromatography Hyphenated with Quadrupole-Time-of-Flight Mass Spectrometry
- Source :
- Molecules, Volume 23, Issue 8, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules, Vol 23, Iss 8, p 1946 (2018)
- Publication Year :
- 2018
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2018.
-
Abstract
- Necrostatins have been shown to retard necroptosis, a programmed necrotic-like cell death, which has been shown to underlie pathophysiology of various diseases. Nec-1s, a novel highly effective necrostatin, overcomes some drawbacks of former necrostatin analogues. The determination of Nec-1s in biological system, however, has not been carried out so far. Therefore, this study was undertaken to optimize and validate the HPLC-DAD-Q-TOF method for the assessment of Nec-1s levels in the plasma what is the necessity for designing its proper dosing regimen for in vivo studies. Benefits of the proposed analytical protocol include: (i) simple sample preparation (precipitation of plasma proteins, evaporation of acetonitrile, reconstitution in mobile phase), (ii) fast, selective and sensitive analysis due to a highly orthogonal LC-MS system providing less than 8 min analysis time, (iii) detection of Nec-1s without any matrix interferences, and quantitation of very low concentration levels of Nec-1s (LLOQ ~ 20 ng/mL), (iv) high reliability of Nec-1s determination with precision and accuracy values meeting the FDA criteria for biomedical analysis. The proposed analytical protocol is suitable for routine use in relevant biological studies, and, in this work, it was successfully applied for monitoring of Nec-1s plasma levels in rats providing reproducible and consistent results. Based on pharmacokinetic features, which can also be assessed due to the results of this study, there will be efforts to perform both acute and chronic in vivo studies and potential clinical safety studies first.
- Subjects :
- 0301 basic medicine
Male
Accuracy and precision
Indoles
high performance liquid chromatography
Pharmaceutical Science
rat plasma
Mass spectrometry
High-performance liquid chromatography
Article
Mass Spectrometry
Analytical Chemistry
lcsh:QD241-441
Matrix (chemical analysis)
03 medical and health sciences
determination
lcsh:Organic chemistry
Pharmacokinetics
In vivo
Limit of Detection
Drug Discovery
Animals
Humans
Physical and Theoretical Chemistry
Quadrupole time of flight
Rats, Wistar
biomedical analysis
Chromatography, High Pressure Liquid
Chromatography
Cell Death
Dose-Response Relationship, Drug
Chemistry
Organic Chemistry
Imidazoles
Reproducibility of Results
Plasma
digestive system diseases
quadrupole-time-of-flight mass spectrometry
030104 developmental biology
Chemistry (miscellaneous)
Molecular Medicine
necrostatin Nec-1s
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....e6c20b01ce8109c6ddd4761787618e16
- Full Text :
- https://doi.org/10.3390/molecules23081946