Quantification of isavuconazole from dried blood spots: Applicability in therapeutic drug monitoring

Dried blood spots (DBS) is a convenient method of blood sampling for biomedical quantification of various drugs. Compared to conventional venipuncture and subsequent plasma measurement, DBS provides advantages in less invasive sampling and easy and safe shipping of samples. The main drawback is the difficult calculation of precise plasma concentrations from the DBS measurements. In this study, a method for the quantification of the antimycotic drug isavuconazole from DBS was developed and its applicability in therapeutic drug monitoring (TDM) was evaluated by comparing the DBS quantification results with the corresponding plasma values. DBS were produced by spotting 15 μL of EDTA-blood onto DBS cards. The whole DBS spots were extracted in methanol:water 10:1, and the extracts were analyzed by an established HPLC method using fluorescence detection. Isavuconazole proved to be stable in DBS over 3 weeks at room temperature or refrigerated at 6 °C. Intra-day precision and accuracies of the quantification from DBS were better than 5 %, while the inter-day results were better than 12 %. Fourteen plasma samples from intensive care patients showing isavuconazole concentrations of <0.1 μg/mL to 3.52 μg/mL (median 1.42 μg/mL) were compared to the results obtained from corresponding DBS samples. All concentration values were covered by the calibration range (0.1-20 μg/mL) of the analytical method. Differences between plasma and DBS results were less than 0.2 μg/mL, with an underestimation of less than 6 % in the DBS values. As these differences were of no therapeutic relevance, DBS could be considered a viable matrix for TDM of isavuconazole in intensive care patients.