therapeutic drug monitoring of voriconazole: comparison of bioassay with high-performance liquid chromatography

Background: voriconazole is a triazole antifungal agent with considerable inter and intra-individual variability in plasma concentrations. therapeutic drug monitoring of voriconazole plays an important role in optimizing the efficacy and safety of the drug in patients. objectives: this study aimed at evaluating the performance of a simple agar well diffusion bioassay and comparing its utility with high-performance liquid chromatography (hplc). methods: the clinical isolate of voriconazole hyper susceptible candida kefyr was used for a simple agar well diffusion bioassay method. acetonitrile precipitations followed by reverse-phase hplc on c18 column, with ultra violet detection, were used for hplc. cross validation was done by evaluating the accuracy and precision of both methods in a large cohort of 180 samples from 60 voriconazole-treated patients. results: the validated bioassay method and hplc, as a reference method, were found to be accurate and precise. a good correlation was found between the 2 methods with similar analytical range (0.25 – 16 µg/ml). the result of linear regression analysis revealed bioassay = 0.961 (hplc) +0.148; r2 = 0.965; correlation coefficient = 0.982; n = 180. voriconazole serum concentration of patients ranged from 0.25 µg/ml to 5.41 µg/ml when using hplc, and from 0.25 µg/ml to 5.71 µg/ml when using the bioassay method. conclusions: when laboratories are not equipped with hplc, bioassay may be a reliable technique with sufficient accuracy and precision for monitoring voriconazole plasma concentration.