Determination of voriconazole in dog plasma by lc-ms/ms and its toxicokinetics / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish a method for the determination of voriconazole in dog plasma and investigate its toxicokinetics. METHODS: After protein precipitation with acetonitrile, voriconazole and fluconazole were separated on an Agilent Poroshell120 EC-C18 column (2.1 mm×50 mm, 2.7 μm), with acetonitrile and water (0.1% FA) as the mobile phase at a flow rate of 0.3 mL·min-1. Detection was carried out by the electrospray positive ionization mass spectrometry in the multiple reacion monitoring (MRM) mode. The MRM transitions of m/z 335.1→281.3 and m/z 307.1→220.0 were used to quantify voriconazole and fluconazole, respectively. Thirty Beagle dogs received intravenous infusion of voriconazole at low, medium and high doses (1, 3, 6 mg·kg-1·d-1) once a day for 12 weeks. RESULTS: The calibration curve was linear over 10-10 000 ng·mL-1 . RSD was less than 15%, and the accuracy was within the range of 85%-115%.The exposure of voriconazole to females was significantly higher than that of males in Beagle dogs. When the dose was 1-6 mg·kg-1·d-1, the exposure of voriconazole to beagle dogs increased with the increase of dose, and the drug did not accumulate. CONCLUSION: The method can be applied to the determination of voriconazole in dog plasma, and is suitable to the toxicokinetics study of voriconazole.