An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin

• Published in: Journal of pharmaceutical analysis Vol. 11; no. 6; pp. 732 - 738
• Main Authors: Yuan, Huiya, Yu, Shihui, Chai, Guihong, Liu, Junting, Zhou, Qi (Tony)
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.12.2021; Xi'an Jiaotong University, Journal of Pharmaceutical Analysis; School of Forensic Medicine,China Medical University,Shenyang,110122,China; Department of Industrial and Physical Pharmacy,College of Pharmacy,Purdue University,West Lafayette.IN,47907,USA%Department of Industrial and Physical Pharmacy,College of Pharmacy,Purdue University,West Lafayette,IN,47907,USA%School of Forensic Medicine,China Medical University,Shenyang,110122,China; Xi'an Jiaotong University; Elsevier
• Subjects: Acetonitrile; Antibiotics; Bronchopulmonary infection; Cell culture; Ciprofloxacin; Colistin; Culture media; Cystic fibrosis; Cytotoxicity; Drug delivery; Drug resistance; Epithelial cells; Formic acid; High-performance liquid chromatography; HPLC-MS/MS; Infections; Ivacaftor; Lung epithelial cells; Lungs; Original; Pathogens; Pharmacokinetics; Plasma; Proteins; Reagents; Transport media; Trifluoroacetic acid; United States > US; China; Plasma; Ivacaftor; Lung epithelial cells; HPLC-MS/MS; Colistin; Cystic fibrosis; Ciprofloxacin
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2021.02.004

Inhaled antibiotics such as colistin and ciprofloxacin are increasingly used to treat bacterial lung infections 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 reaction 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 B1 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. [Display omitted] •The method is highly useful for analysis on cytotoxicity, pharmacokinetics, and in vitro drug delivery for cystic fibrosis.•The method is the first validated method for analysis of colistin, ivacaftor and ciprofloxacin simultaneously.•The method could be employed in analysis of plasma, epithelial cell, cell culture medium, and drug transport media.•Trifluoroformic acid was used as a drug-protein bond cleavage, and formic acid was added to increase the response of drugs.•The method could detect the three model drugs within 6 min.