Determination of Voriconazole Concentrations in Serum by GC-MS

摘要

Background: Voriconazole is a broad spectrum triazole antifungal drug used to treat systemic fungal infections. Therapeutic drug monitoring of voriconazole is necessary for achieving maximal efficiency without inducing toxic side effects. Other publications have reported methods for measuring voriconazole in serum using high-performance liquid chromatography (HPLC) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Here, we report for the first time a method for the measurement of voriconazole in serum samples using gas chromatography mass spectrometry (GC-MS). Methods: Protein precipitation with methanol was used to extract the antifungal that was derivatized with BSTFA (Sigma-Aldrich, St. Louis, MO) and analyzed by GC-MS. Linearity, sensitivity, precision, accuracy, and drug interferences were evaluated for this assay. Results: Our method was linear up to 10 mu g/ml of voriconazole. The LOQ was determined to be 0.4 mu g/ml. CV for between-day precision was <12%. Correlation with an established LC-MS/MS yielded a R2 of 0.96. Tested drugs did not result in >10% error in measurement. Conclusion: To our knowledge, we report here the first GCMS method for voriconazole measurement with acceptable performance. We hope that this method allows clinical laboratories without HPLC or LC-MS/MS instrumentation to measure voriconazole. (C) 2015 Wiley Periodicals, Inc.