An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin,ivacaftor and ciprofloxacin
- Author:
Huiya YUAN
1
,
2
;
Shihui YU
;
Guihong CHAI
;
Junting LIU
;
(tony)-Qi ZHOU
Author Information
1. School of Forensic Medicine,China Medical University,Shenyang,110122,China
2. Department of Industrial and Physical Pharmacy,College of Pharmacy,Purdue University,West Lafayette.IN,47907,USA
- Keywords:
Cystic fibrosis;
Ivacaftor;
Colistin;
Ciprofloxacin;
HPLC-MS/MS;
Lung epithelial cells;
Plasma
- From:
Journal of Pharmaceutical Analysis
2021;11(6):732-738
- CountryChina
- Language:Chinese
-
Abstract:
Inhaled antibiotics such as colistin and ciprofloxacin are increasingly used to treat bacterial lung in-fections in cystic fibrosis patients.In this study,we established and validated a new HPLC-MS/MS method that could simultaneously detect drug concentrations of ciprofloxacin,colistin and ivacaftor in rat plasma,human epithelial cell lysate,cell culture medium,and drug transport media.An aliquot of 200 μL drug-containing rat plasma or cell culture medium was treated with 600 μL of extraction solution(acetonitrile containing 0.1% formic acid and 0.2% trifluoroacetic acid (TFA)).The addition of 0.2% TFA helped to break the drug-protein bonds.Moreover,the addition of 0.1% formic acid to the transport medium and cell lysate samples could significantly improve the response and reproducibility.After vortexing and centrifuging,the sample components were analyzed by HPLC-MS/MS.The multiple re-action monitoring mode was used to detect the following transitions:585.5-101.1 (colistin A),578.5-101.1 (colistin B),393.2-337.2 (ivacaftor),332.2-314.2 (ciprofloxacin),602.3-101.1 (polymyxin 81 as internal standard (IS)) and 595.4-101.1 (polymyxin B2 as IS).The running time of a single sample was only 6 min,making this a time-efficient method.Linear correlations were found for colistin A at 0.029-5.82 μg/mL.colistin B at 0.016-3.14 μg/mL.ivacaftor at 0.05-10.0 μg/mL,and ciprofloxacin at 0.043-8.58 μg/mL.Accuracy,precision,and stability of the method were within the acceptable range.This method would be highly useful for research on cytotoxicity,animal pharmacokinetics,and in vitro drug delivery.