药代动力学
色谱法
化学
蛋白质沉淀
串联质谱法
选择性反应监测
肽
液相色谱-质谱法
生物利用度
质谱法
萃取(化学)
高效液相色谱法
定量分析(化学)
作者
Lili Jin,Haibo Ding,Volkan Degirmenci,Hongchuan Xin,Qifan Miao,Qiu Yu Wang,Dianbao Zhang
出处
期刊:Molecules
[MDPI AG]
日期:2021-12-24
卷期号:27 (1): 92-92
标识
DOI:10.3390/molecules27010092
摘要
AWRK6 was a synthesized peptide developed based on the natural occurring peptide dybowskin-2CDYa, which was discovered in frog skin in our previous study. Here, a quantitative determination method for AWRK6 analysis in rat plasma by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated following U.S. FDA guidelines. A combination of plasma precipitation and liquid–liquid extraction was applied for the extraction. For pharmacokinetics study, the rats were administrated with AWRK6 via intraperitoneal and intravenous injection. The prepared plasma samples were separated on an ODS column and analyzed by tandem MS using precursor-to-product ion pairs of m/z: 533.4→84.2 for AWRK6 and m/z: 401.9→101.1 for internal standard Polymyxin B sulfate in multiple reaction monitoring mode. AWRK6 concentrations in rat plasma peaked at about 1.2 h after intraperitoneal injections at 2.35, 4.7 and 9.4 mg/kg bodyweight. The terminal half-life was around 2.8 h. The absolute bioavailability of AWRK6 was 50% after 3 doses via injection, and the apparent volume of distribution was 4.884 ± 1.736 L. The obtained determination method and pharmacokinetics profiles of AWRK6 provides a basis for further development, and forms a benchmark reference for peptide quantification.
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