High Performance Liquid Chromatography Coupling with Photo-diode Array Detector Method for Monitoring Voriconazole and Its Main Metabolite N-oxidized Voriconazole and Its Application to Medication Guidance for Childhood Leukemia / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a method for simultaneous determination of voriconazole and its main metabolite N-oxidized voriconazole in blood, and monitor the levels of voriconazole and N-oxidized voriconazole in leukemia children aged 2-12 years. METHODS: Agilent ZORBAX SB-C18 column (4.6 mm×250 mm,5 μm) was used, and the mobile phase was acetonitrile, methanol and ammonium acetate buffer (10 mmol•L-1, pH adjusted with acetic acid to 3.0)=27∶23∶50, the flow rate was 1 mL•min-1, and the wavelength was set at 262 nm. The sample was extracted with ethyl acetate.Carbamazepine was used as the internal standard. RESULTS: The calibration curves of voriconazole and N-oxidized voriconazole were linear in the range of 0.1-8.0 μg•mL-1, the lower limit of quantitation was 0.1 μg•mL-1, and the intra-assay and inter-assay precision RSDs were between 2% and 10%. The accuracy, method recovery and stability all met the requirements.Twenty-nine patients were monitored with a total of 100 blood samples.The medians (IQRs) of voriconazole concentration, N-oxidized voriconazole concentration, and ratio of N-oxidized voriconazole to voriconazole were 0.87 μg•mL-1 (0.32-1.65 μg•mL-1) and 1.15 μg•mL-1 (0.55-1.67 μg•mL-1) and 1.10(0.66-1.22), respectively. There was a correlation relationship between the concentrations of voriconazole and N-oxidized voriconazole (r=0.603 1, P<0.000 1). CONCLUSION: The method is simple, accurate, highly specific, and can simultaneously monitor the concentrations of voriconazole and N-oxidized voriconazole, thus can be used for the pharmacokinetic research of voriconazole and clinical drug monitoring.