title: Development and validation of an HPLC-UV method for pazopanib quantification in human plasma and application to patients with cancer in routine clinical practice.
abstract: BACKGROUND
  Pazopanib, a new oral angiogenesis inhibitor, has demonstrated clinical activity against multiple solid tumors and was approved for the treatment of patients with advanced renal cell carcinoma. As an exposure-response relationship has been observed for pazopanib, its therapeutic drug monitoring could be a valuable tool in clinical practice. Therefore, the aim of this study was to develop and validate a selective and precise high performance liquid chromatography-ultraviolet method for the measurement of pazopanib in plasma from patients with cancer.
  
  
  METHODS
  After liquid-liquid extraction with diethyl ether, pazopanib and gefitinib (internal standard) were separated using isocratic elution on an Ultrabase C18 column using a mobile phase consisting of a mixture in vol/vol proportion of 47:53 of ammonium acetate (pH, 7; 0.02 mol/L) and acetonitrile/methanol (70:30, vol/vol) pumped at a constant flow rate of 1 mL/min. Quantification was performed at 260 nm. Method validation was undertaken as per the guidelines for Bioanalytical Method Validation published by the Food and Drug Administration and European Medicines Agency.
  
  
  RESULTS
  Calibration curves were linear over the range 0.5-100 mcg/mL. Interday and intraday coefficients of variations were less than 4.5%. The limit of detection and the lower limit of quantification were 0.2 and 0.5 mcg/mL, respectively. Recovery of pazopanib from plasma was >80%.
  
  
  CONCLUSIONS
  This is the first high performance liquid chromatography-ultraviolet method for pazopanib quantification that has been validated within a wide range of plasma concentrations and is a suitable method for therapeutic drug monitoring of pazopanib.
authors: *Platform of Oncology, Hospital Quirón Torrevieja; †Cathedra of Multidisciplinary Oncology, UCAM Catholic University of San Antonio, Murcia; ‡Pharmacokinetics and Drug Metabolism, AMGEN, Valencia; and §Consulting Projects for Research, Puzol, Spain.
authors: Vanesa
authors: V
authors: Escudero-Ortiz
authors: Juan J
authors: JJ
authors: Pérez-Ruixo
authors: Belén
authors: B
authors: Valenzuela
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007191:Indazoles; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D009369:Neoplasms / Q000188:drug therapy; D011743:Pyrimidines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013449:Sulfonamides / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib