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Molecules 2018, 23(8), 1946; https://doi.org/10.3390/molecules23081946

Determination of Novel Highly Effective Necrostatin Nec-1s in Rat Plasma by High Performance Liquid Chromatography Hyphenated with Quadrupole-Time-of-Flight Mass Spectrometry

1
Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovak Republic
2
Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovak Republic
3
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Odbojárov 10, 832 32 Bratislava, Slovak Republic
*
Author to whom correspondence should be addressed.
Received: 19 July 2018 / Revised: 1 August 2018 / Accepted: 2 August 2018 / Published: 3 August 2018
(This article belongs to the Section Analytical Chemistry)
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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. View Full-Text
Keywords: high performance liquid chromatography; quadrupole-time-of-flight mass spectrometry; necrostatin Nec-1s; rat plasma; determination; biomedical analysis high performance liquid chromatography; quadrupole-time-of-flight mass spectrometry; necrostatin Nec-1s; rat plasma; determination; biomedical analysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Mikuš, P.; Pecher, D.; Rauová, D.; Horváth, C.; Szobi, A.; Adameová, A. Determination of Novel Highly Effective Necrostatin Nec-1s in Rat Plasma by High Performance Liquid Chromatography Hyphenated with Quadrupole-Time-of-Flight Mass Spectrometry. Molecules 2018, 23, 1946.

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