Determination of fluoroquinolones in dried plasma spots by using microwave-assisted extraction coupled to ultra-high performance liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring

摘要

Therapeutic drug monitoring is important for achieving desirable outcomes in tuberculosis treatment. In this study, microwave-assisted extraction was used to extract levofloxacin, ciprofloxacin, and moxifloxacin from dried plasma spots for subsequent detection and quantification with ultra-high performance liquid chromatography-tandem mass spectrometry. Dried plasma spotting was performed by dropping 15 mu L of plasma on a protein saver card. Analyte extraction was performed with microwave-assisted extraction at 400 W for 40 s in 90 % methanol. Samples were analyzed with a core-shell C18 column (100 mm x 2.1 mm, 2.6 mu m, 100 angstrom). Multiple reaction monitoring was used and the ion source was operated in positive electrospray ionization mode. The correlation coefficients of the calibration curves were > 0.999 for all three drugs over a range of 0.2-20 mu g/mL. The intraday precision (n = 5) of the peak area ratios of the analyte to the internal standard was between 1.3 and 4.0 % relative standard deviation (RSD). The intraday accuracy ranged from 93.6-106.9%. The interday (n = 3) precision of the peak area ratios ranged from 1.9 to 8.8 % RSD, and the accuracy ranged from 94.9-107.1%. Regarding clinical application, the quantification results for moxifloxacin from dried plasma spots (DPSs) were strongly similar to the results from the plasma samples, which showed that Pearson's rho > 0.949. The validation and application results showed that the developed method can be used as an efficient analytical technique for therapeutic drug monitoring of fluoroquinolones for patients with tuberculosis. (C) 2020 Elsevier B.V. All rights reserved.