title: Rapid simultaneous determination of voriconazole and its N-oxide in human plasma using an isocratic high-performance liquid chromatography method and its clinical application.
abstract: OBJECTIVE
  The aim of this study was to develop a simultaneous determination method for voriconazole (VRCZ) and its N-oxide (VNO) in human plasma and to apply it to clinical samples.
  
  
  METHODS
  Plasma specimens were deproteinized with acetonitrile and then injected into an HPLC-UV system. VRCZ and VNO were separated on an ODS column filled with 2.3-μm particles using an isocratic mixture of acetonitrile/methanol/phosphate buffer 25/10/65 (v/v/v). Plasma concentrations of VRCZ and VNO in 25 patients were determined.
  
  
  RESULTS
  Both VRCZ and VNO were linear (r>0.999) over the concentration ranges of 0.1-8.0mg/L. The run time for quantification of the analytes was 4 min. Interindividual variation in the plasma concentration of VRCZ that ranged from less than 0.1 to 6.96 mg/L was observed. VNO concentrations weakly depended on VRCZ dosage.
  
  
  CONCLUSIONS
  The present method can contribute to the optimization of antifungal therapy using VRCZ.
authors.affiliation: Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431–3192, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamada
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Mino
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yagi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Naito
authors.forename: Junichi
authors.initials: J
authors.lastname: Kawakami
mesh_terms: D000097:Acetonitriles / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008956:Models, Chemical; D010087:Oxides / Q000097:blood; D010949:Plasma / Q000378:metabolism; D011743:Pyrimidines / Q000032:analysis / Q000097:blood*; D015203:Reproducibility of Results; D013997:Time Factors; D014230:Triazoles / Q000032:analysis / Q000097:blood*; D014466:Ultraviolet Rays; D065819:Voriconazole
chemical_list: D000097:Acetonitriles; D000935:Antifungal Agents; D010087:Oxides; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole; C032159:acetonitrile