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

Abstract

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.

Challenges of Colistin Use in ICU and Therapeutic Drug Monitoring: A Literature Review

“…The most frequently mentioned product ion corresponds to values in the range m / z 100.9–101.4 [ 26 , 27 ]. The product ions and a summary of the selected methods are listed in Table 1 [ 17 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ].…”

A quantitative method for determination of colistin E2 methane sulphonate sodium (CMS E2) in human plasma by 15N-labeled colistin E2

“…To accurately quantify in vivo pharmacokinetics of CMS E2, speed up its listing, and bene t clinical patients, it is critical to develop a method for more accurate quantitative detection of CMS E2 in human plasma. In recent years, several methods, such as weak cationic solid phase extraction, hydrophiliclipophilic-balanced solid phase extraction, post-column derivatization, and in-line molecularly imprinted solid-phase extraction combined with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), have been used for the determination of colistin and CMS in biological samples [7][8][9][10][11] . However, the ISs used in the above studies were analogs of the subject to test (polymyxin B1/B2) or polymyxin B (a mixture).…”

HPLC Determination of Colistin in Human Urine Using Alkaline Mobile Phase Combined with Post-Column Derivatization: Validation Using Accuracy Profiles

“…The advantages and disadvantages of these approaches in terms of cost, instrumentation, matrix interferences, and sensitivity are more or less well known, and they were adequately discussed in a recent dedicated review article by Gikas and coworkers [ 3 ]. Mass spectrometric detection techniques are always attractive in bioanalysis, and there have been several very recent reports on the analysis of Colistin in rats [ 9 , 10 ] or human plasma [ 11 ], intestinal matrices of poultry [ 12 , 13 , 14 ], and eggs [ 15 ]. Sample preparation prior to LC–MS analysis varies from simple protein precipitation [ 9 ] to solid-phase extraction using advanced cation exchange or hydrophilic/lipophilic balance (HLB) materials [ 10 , 14 ].…”

“…Mass spectrometric detection techniques are always attractive in bioanalysis, and there have been several very recent reports on the analysis of Colistin in rats [ 9 , 10 ] or human plasma [ 11 ], intestinal matrices of poultry [ 12 , 13 , 14 ], and eggs [ 15 ]. Sample preparation prior to LC–MS analysis varies from simple protein precipitation [ 9 ] to solid-phase extraction using advanced cation exchange or hydrophilic/lipophilic balance (HLB) materials [ 10 , 14 ]. Typically, such methods are capable of detecting Colistin at the low ppm to ppb levels.…”