Therapeutic drug monitoring of voriconazole: validation of a high performance liquid chromatography method and comparison with an ARK immunoassay

Abstract

ObjectiveVoriconazole is an antifungal agent used in the treatment of aspergillosis and fluconazole-resistant Candida infections. Therapeutic drug monitoring (TDM) of voriconazole is recommended to optimise clinical results. The aim of this study was the development and validation of a high performance liquid chromatography (HPLC) method for measuring voriconazole in human serum, and comparison with an ARK immunoassay method.MethodsLinearity, precision, accuracy and stability of the HPLC method were validated according to the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. The method was applied to the analysis of 58 trough serum samples from patients treated with voriconazole, and the HPLC-UV (ultraviolet) method was compared with an ARK immunoassay. The correlation of both methods was studied by the Pearson regression coefficient and the concordance of the values was evaluated by the Bland-Altman and Passing-Bablok methods.ResultsAll validation parameters met the criteria set out in the FDA and EMA guidelines. The standard curve was linear over a concentration range of 0.25–16 µg/mL with a limit of quantification of 0.125 µg/mL. No interactions between voriconazole and other drugs was observed and voriconazole was stable after 1 month at −80°C. Comparison of the HPLC method and the enzyme immunoassay method showed a linear correlation with a systematic error of −0.61 µg/mL between both methods.ConclusionThe method developed is simple and fast and can be easily applied for routine therapeutic drug monitoring of voriconazole. The HPLC-UV method was more sensitive than the immunoassay method and there was concordance with the immunoassay. Consequently both methods could be used, considering the correlation between them.

Comparison of ultra-performance liquid chromatography and ARK immunoassay for therapeutic drug monitoring of voriconazole

“…5 An overestimation was observed with the ARK TM immunoassay, which has also been described when this immunoassay is applied on other analysers. 3,4,6 According to our study, in most samples, both techniques led to similar dose recommendations. Nonetheless, they could differ with concentrations near the lower limit of the therapeutic range, leading to no change in patients who would need an increase of dose when the enzyme immunoassay is used.…”

Determination of Voriconazole in Human Plasma by Liquid Chromatography Tandem Mass Spectrometry: Application in Therapeutic Drug Monitoring

“…However, a low concentration of voriconazole in plasma is associated with treatment failure in patients with an invasive infection, which may lead to devastating consequences [18]. Therapeutic Drug Monitoring (TDM) of voriconazole is recommended for patients treated with voriconazole through measuring the plasma trough level to improve the clinical outcomes, avoid adverse events and improve drug efficacy [19] [20].…”

Two methods for therapeutic drug monitoring of voriconazole: act according to circumstances

“…In the recently published study by Blanco-Dorado et al, 1 the authors described two methods for determining plasma concentrations of voriconazole: high performance liquid chromatography (HPLC) and an ARK immunoassay. After correlation of the two methods and the concordance of the values was evaluated, it was noted that both methods could be implemented for therapeutic drug monitoring (TDM) of voriconazole to avoid hepatotoxicity and enable continued effective therapy for patients with invasive fungal infections.…”

“…We agree with the authors’ conclusion that HPLC is more sensitive than the immunoassay method. The inspiring outcomes from the study of Blanco-Dorado et al 1 will encourage pharmacists to choose different analytical methods in different situations.…”