Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 95, Issue -, Pages 1479-1485Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2017.09.063
Keywords
Necrostatin-1; Necroptosis inhibitor; LC-MS/MS; Pharmacokinetics; Bioavailability
Funding
- Capital Special Projects of Chinese Medicine [14ZY16]
Ask authors/readers for more resources
Necrostatin-1 (Nec-1) is known as a specific and potent inhibitor of non-apoptotic cell death. In this study, a rapid and sensitive LC-MS/MS method that was developed for the determination of Nec-1 levels in plasma. Meanwhile, it has been used to explore pharmacokinetics and bioavailability of Nec-1 among rats. The m/z 260.1 -> 131 was selected as the optimal MRM transition in analyzing Nce-1. The chromatographic separation was performed with SB-C18 analytical column using the optimized gradient elution mode. The extraction recoveries of Nec-1 ranged from 85.40% to 98.25% and the matrix effects were between 94.73% and 99.26%. Both the intra-and inter-day precision did not exceed 10.0%, respectively. Moreover, it is found that Nec-1 remained stable in plasma despite different processing and storage environment. The plasma concentration of Nec-1 was successfully determined among rats who received single dose via intravenous and oral route (5 mg/kg), respectively. A two-compartment model was fitted the concentration-time profile of the Nec-1 with C-max 1733 mu g L-1 and t(1/2) 1.8 h for intravenous route, and C-max 648 mu g L-1 and t(1/2) 1.2 h for oral route, respectively. The results showed that absolute bioavailability of Nec-1 was 54.8%. It is promising that the study is helpful to understand in vivo behaviors of Nec-1 and facilitate the future investigations of the compound.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available