title: Development and validation of an HPLC-UV method for sorafenib quantification in human plasma and application to patients with cancer in routine clinical practice.
abstract: BACKGROUND
  Several factors such as low therapeutic index, large interindividual variability in systemic exposure, and the relationships between exposure and toxicity for sorafenib could justify its therapeutic drug monitoring (TDM). To support TDM, a selective and precise high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed and validated for the determination of sorafenib in human plasma.
  
  
  METHODS
  After protein precipitation with acetonitrile, sorafenib and lapatinib (internal standard) were separated using isocratic elution on a Kromasil C18 column using a mobile phase of acetonitrile and 20 mmol/L ammonium acetate in a proportion 53:47 (vol/vol) pumped at a constant flow rate of 1.2 mL/min. Quantification was performed at 260 nm. Validation experiments were carried out after the guidelines for Bioanalytical Method Validation published by the Food and Drug Administration and the European Medicines Agency.
  
  
  RESULTS
  Calibration curves were linear over the range 0.1-20 mcg/mL. Inter- and intra-day coefficients of variation were <3%. The limit of detection and the lower limit of quantification were 0.06 and 0.1 mcg/mL, respectively. Recoveries of sorafenib from plasma were >99% in all cases.
  
  
  CONCLUSIONS
  This method was successfully applied to the determination of the drug in the plasma of 2 patients with cancer receiving sorafenib 200 and 400 mg orally twice daily, respectively, and could be useful for TDM of sorafenib in routine clinical practice.
authors.affiliation: *Platform of Oncology, Hospital Quirón Torrevieja, Torrevieja; †Pharmacokinetics and Drug Metabolism, AMGEN, Valencia; and ‡Cathedra of Multidisciplinary Oncology, UCAM Universidad San Antonion de Murcia, Spain.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Escudero-Ortiz
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Pérez-Ruixo
authors.forename: Belén
authors.initials: B
authors.lastname: Valenzuela
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D000077341:Lapatinib; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000188:drug therapy*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D010671:Phenylurea Compounds / Q000097:blood* / Q000493:pharmacokinetics*; D011799:Quinazolines; D015203:Reproducibility of Results; D000077157:Sorafenib; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D011799:Quinazolines; D000077341:Lapatinib; D009536:Niacinamide; D000077157:Sorafenib