Author:
Xu Hongjiang,Li Yanan,Zhang Jing,Zhang Jinhua,Lu Jianguang,Zhang Xiquan,Yang Ling,Zhao Wenjie,Feng Jun
Abstract
AbstractThe single-component colistin E2, with superior antibacterial activity and lower toxicity, was being developed as the latest generation of polymyxin drugs. However, colistin E2 has not been tested quantitatively in biological matrices. In this study, based on the quantitative detection of colistin methanesulphonate (CMS) and colistin by Zhao et al., 15N-labeled colistin E2 was used as an internal standard (IS) for a more accurate quantitative detection of CMS E2 in human plasma. A rapid ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) assay method was developed for determination of CMS E2 and colistin E2 in human plasma. After pretreatment of plasma samples by 96-well SPE Supra-Clean Weak Cation Exchange (WCX) plate, the formed colistin E2 was detected and quantified by UHPLC–MS/MS system. All plasma lots were found to be free of interferences with the analyte. The matrix has no effect on the quantitation of the analyte. No significant effect of the carryover was observed. The dilution integrity was demonstrated in plasma samples without the loss of accuracy and precision. The lower limit of quantification (LLOQ) was 0.0300 mg/L for colistin E2 in plasma with accuracy (relative error, 5.1–12.7%) and precision (relative standard deviation, − 5.7–9.3%). Stability of CMS E2 and colistin E2 was demonstrated in biological samples before and during sample treatment, and in the extract. Furthermore, this method was successfully applied to the analysis of plasma samples obtained from Chinese healthy volunteers receiving a single intravenous CMS E2 dose of 5 mg/kg. In conclusion, the detection method was characterized by speed and high accuracy, which laid a solid foundation for the subsequent development of CMS E2 drug.
Funder
Program of Shanghai Academic/Technology Research Leader
Publisher
Springer Science and Business Media LLC
Reference17 articles.
1. Ventola, C. L. The antibiotic resistance crisis: Part 1: Causes and threats. P T. 40(4), 277–283 (2015).
2. Tacconelli, E. et al. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 18, 318–327 (2018).
3. Nation, R. L. Polymyxin antibiotics: From laboratory bench to bedside. Adv. Exp. Med. Biol. 1145, 1145 (2019).
4. Bergen, P. J., Li, J., Rayner, C. R. & Nation, R. L. Colistin methanesulfonate is an inactive prodrug of colistin against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 50, 1953–1958 (2006).
5. Nation, R. L., Velkov, T. & Li, J. Colistin and polymyxin B: Peas in a pod, or chalk and cheese?. Clin. Infect. Dis. 59, 88–94 (2014).