title: Development and Validation of Voriconazole Concentration by LC-MS-MS: Applied in Clinical Implementation.
abstract: BACKGROUND
  Voriconazole (VRZ) is a triazole antifungal used for treatment of invasive fungal infection, which is a life-threatening condition. Therapeutic drug monitoring is recommended for identifying the optimal dose in patients who have hepatic/renal impairment or reduced function of the CYP2C19 metabolizing enzyme.
  
  
  METHODS
  One hundred microliters of sample plasma was extracted by protein precipitated with 200 μl of acetonitrile containing fluconazole as internal standard (IS). After vortexing and centrifugation, supernatant was dried and reconstituted with 100 μl of mobile phase (ACN: 0.1% formic acid in 10 mM Ammonium acetate) (50:50 v/v) before injected. The column was C18, 2.7 μm, 3.0 × 50 mm at flow rate of 0.5 ml/min with retention time of 0.5 and 0.75 min for VRZ and IS, respectively. The tandem mass spectrometer was set in multiple reactions monitoring (MRM) mode with the following transition; VRZ m/z 350.10→281.10 and 307.20→220.20 (IS).
  
  
  RESULTS
  The accuracy and precision inter- and intra-day were less than 9%, over the range 0.05-10 μg/ml. The linearity was consistent (r2= 0.9987) and recovery was more than 85.0% for both analyses.
  
  
  CONCLUSIONS
  This method is applicable for routine monitoring of patients' VRZ plasma level with fast and accurate runtime to assess CYP2C19 genotype.
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Santirat
authors.initials: S
authors.lastname: Prommas
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Apichaya
authors.initials: A
authors.lastname: Puangpetch
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Nuttawut
authors.initials: N
authors.lastname: Jenjirattithigarn
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Sumonrat
authors.initials: S
authors.lastname: Chuwongwattana
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Thawinee
authors.initials: T
authors.lastname: Jantararoungtong
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Napatrupron
authors.initials: N
authors.lastname: Koomdee
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Siwalee
authors.initials: S
authors.lastname: Santon
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Montri
authors.initials: M
authors.lastname: Chamnanphon
authors.affiliation: Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.|Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center (SDMC), Ramathibodi Hospital, Bangkok, Thailand.
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D065731:Cytochrome P-450 CYP2C19 / Q000378:metabolism; D006801:Humans; D010641:Phenotype; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*; D065819:Voriconazole / Q000032:analysis* / Q000097:blood / Q000737:chemistry
chemical_list: D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
keywords: LC-MS/MS; antifungal; applications; genetics; quantitative