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

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 ivacaft...

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Main Authors: Huiya Yuan, Shihui Yu, Guihong Chai, Junting Liu, Qi (Tony) Zhou
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Journal of Pharmaceutical Analysis
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2095177921000198
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author Huiya Yuan
Shihui Yu
Guihong Chai
Junting Liu
Qi (Tony) Zhou
author_facet Huiya Yuan
Shihui Yu
Guihong Chai
Junting Liu
Qi (Tony) Zhou
author_sort Huiya Yuan
collection DOAJ
description 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.
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spelling doaj.art-fd9ad196c1604c2289aab67258bb01942022-12-21T18:12:50ZengElsevierJournal of Pharmaceutical Analysis2095-17792021-12-01116732738An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacinHuiya Yuan0Shihui Yu1Guihong Chai2Junting Liu3Qi (Tony) Zhou4School of Forensic Medicine, China Medical University, Shenyang, 110122, China; Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USADepartment of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USADepartment of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USASchool of Forensic Medicine, China Medical University, Shenyang, 110122, China; Corresponding author.Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University, West Lafayette, IN, 47907, USA; Corresponding author.;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.http://www.sciencedirect.com/science/article/pii/S2095177921000198Cystic fibrosisIvacaftorColistinCiprofloxacinHPLC-MS/MSLung epithelial cells
spellingShingle Huiya Yuan
Shihui Yu
Guihong Chai
Junting Liu
Qi (Tony) Zhou
An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
Journal of Pharmaceutical Analysis
Cystic fibrosis
Ivacaftor
Colistin
Ciprofloxacin
HPLC-MS/MS
Lung epithelial cells
title An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
title_full An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
title_fullStr An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
title_full_unstemmed An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
title_short An LC-MS/MS method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin, ivacaftor and ciprofloxacin
title_sort lc ms ms method for simultaneous analysis of the cystic fibrosis therapeutic drugs colistin ivacaftor and ciprofloxacin
topic Cystic fibrosis
Ivacaftor
Colistin
Ciprofloxacin
HPLC-MS/MS
Lung epithelial cells
url http://www.sciencedirect.com/science/article/pii/S2095177921000198
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