title: Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS.
abstract: BACKGROUND
  Pazopanib is approved for the treatment of renal cell carcinoma and soft tissue sarcoma. Analyses show increased benefit in patients with plasma trough concentrations ≥20.5 μg/ml compared with patients with lower concentrations.
  
  
  RESULTS
  We developed a DBS assay as a patient friendly approach to guide treatment. The method was validated according to US FDA and EMA guidelines and European Bioanalysis Forum recommendations. Influence of spot homogeneity, spot volume and hematocrit were shown to be within acceptable limits. Analysis of paired clinical samples showed a good correlation between the measured plasma and DBS concentrations (R(2) of 0.872).
  
  
  CONCLUSIONS
  The method was successfully validated, applied to paired clinical samples and is suitable for application to therapeutic drug monitoring of pazopanib.
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Remy B
authors.initials: RB
authors.lastname: Verheijen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Sander
authors.initials: S
authors.lastname: Bins
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Thijssen
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Hilde
authors.initials: H
authors.lastname: Rosing
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Lianda
authors.initials: L
authors.lastname: Nan
authors.affiliation: Department of Medical Oncology & Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.|Department of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Ron H J
authors.initials: RH
authors.lastname: Mathijssen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Martijn P
authors.initials: MP
authors.lastname: Lolkema
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.|Department of Pharmaceutical Sciences, Utrecht University, Universiteitsweg 99, 3584 CG, Utrecht, The Netherlands.
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.affiliation: Department of Medical Oncology & Clinical Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.|Department of Medical Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
authors.forename: Neeltje
authors.initials: N
authors.lastname: Steeghs
authors.affiliation: Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
authors.forename: Alwin D R
authors.initials: AD
authors.lastname: Huitema
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D059788:Dried Blood Spot Testing / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007191:Indazoles; D011743:Pyrimidines / Q000097:blood*; D013449:Sulfonamides / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; C516667:pazopanib
keywords: DBS; PK; clinical validation; pazopanib; therapeutic drug monitoring