Validation of an HPLC-UV method for sorafenib determination in human plasma and application to cancer patients in routine clinical practice

J Pharm Biomed Anal. 2009 May 1;49(4):1109-14. doi: 10.1016/j.jpba.2009.02.008. Epub 2009 Feb 20.


Sorafenib, a new oral multikinase inhibitor with antiangiogenic properties, has demonstrated preclinical and clinical activity against several tumor types. The aims of this study were to validate a method for the measurement of sorafenib in plasma from cancer patients, then to test this method in clinical practice. Following liquid-liquid extraction, the compounds were separated with gradient elution (on a C18 ultrasphere ODS column using a mobile phase of acetonitrile/20 mM ammonium acetate), then detected at 255 nm. The calibration was linear in the range 0.5-20 mg/L. Intra- and inter-assay precision was lower than 7 and 10%, respectively, at 0.5, 3 and 20 mg/L. Plasma sorafenib concentrations were measured in 22 cancer patients (99 samples). The mean trough sorafenib concentration (C(min)) and concentration at peak were 4.3+/-2.5 mg/L (n=68, CV=57.5%) and 6.2+/-3.0 mg/L (n=31, CV=47.5%), respectively. Mean sorafenib C(min) in eight patients who experienced grade 3 drug-related adverse events was approximately 1.5-fold greater than that observed in the remaining patients (7.7+/-3.6 mg/L vs. 4.4+/-2.4 mg/L, P=0.0083). In conclusion, the method was successfully used in routine practice to monitor plasma concentrations of sorafenib in cancer patients. Finally, large interindividual variability and higher exposure in patients experiencing severe toxicity support the need for therapeutic drug monitoring to ensure an optimal exposure to sorafenib.

MeSH terms

  • Aged
  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / blood*
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / blood*
  • Antineoplastic Agents / therapeutic use
  • Benzenesulfonates / adverse effects
  • Benzenesulfonates / blood*
  • Benzenesulfonates / therapeutic use
  • Calibration
  • Chromatography, High Pressure Liquid
  • Drug Monitoring
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / blood*
  • Neoplasms / drug therapy
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / adverse effects
  • Pyridines / blood*
  • Pyridines / therapeutic use
  • Quality Control
  • Reference Standards
  • Reproducibility of Results
  • Sorafenib
  • Specimen Handling
  • Spectrophotometry, Ultraviolet


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Benzenesulfonates
  • Phenylurea Compounds
  • Pyridines
  • Niacinamide
  • Sorafenib