Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS

Remy B. Verheijen; Sander Bins; Bas Thijssen; Hilde Rosing; Lianda Nan; Jan H.M. Schellens; Ron H.J. Mathijssen; Martijn P. Lolkema; Jos H. Beijnen; Neeltje Steeghs; Alwin D.R. Huitema

doi:10.4155/bio.15.235

Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS

Remy B. Verheijen^*
, Sander Bins
, Bas Thijssen
, Hilde Rosing
, Lianda Nan
, Jan H.M. Schellens
, Ron H.J. Mathijssen
, Martijn P. Lolkema
, Jos H. Beijnen
, Neeltje Steeghs
, Alwin D.R. Huitema

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

5 Citations (Scopus)

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. Methods & 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 (R² of 0.872). Conclusion: The method was successfully validated, applied to paired clinical samples and is suitable for application to therapeutic drug monitoring of pazopanib.

Original language	English
Pages (from-to)	123-134
Number of pages	12
Journal	Bioanalysis
Volume	8
Issue number	2
DOIs	https://doi.org/10.4155/bio.15.235
Publication status	Published - 1 Jan 2016

Keywords

clinical validation
DBS
pazopanib
PK
therapeutic drug monitoring

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10.4155/bio.15.235

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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. Methods \& 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 (R2 of 0.872). Conclusion: The method was successfully validated, applied to paired clinical samples and is suitable for application to therapeutic drug monitoring of pazopanib.",

keywords = "clinical validation, DBS, pazopanib, PK, therapeutic drug monitoring",

author = "Verheijen, \{Remy B.\} and Sander Bins and Bas Thijssen and Hilde Rosing and Lianda Nan and Schellens, \{Jan H.M.\} and Mathijssen, \{Ron H.J.\} and Lolkema, \{Martijn P.\} and Beijnen, \{Jos H.\} and Neeltje Steeghs and Huitema, \{Alwin D.R.\}",

year = "2016",

month = jan,

day = "1",

doi = "10.4155/bio.15.235",

language = "English",

volume = "8",

pages = "123--134",

journal = "Bioanalysis",

issn = "1757-6180",

publisher = "Taylor and Francis Ltd.",

number = "2",

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TY - JOUR

T1 - Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS

AU - Verheijen, Remy B.

AU - Bins, Sander

AU - Thijssen, Bas

AU - Rosing, Hilde

AU - Nan, Lianda

AU - Schellens, Jan H.M.

AU - Mathijssen, Ron H.J.

AU - Lolkema, Martijn P.

AU - Beijnen, Jos H.

AU - Steeghs, Neeltje

AU - Huitema, Alwin D.R.

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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. Methods & 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 (R2 of 0.872). Conclusion: The method was successfully validated, applied to paired clinical samples and is suitable for application to therapeutic drug monitoring of pazopanib.

AB - 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. Methods & 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 (R2 of 0.872). Conclusion: The method was successfully validated, applied to paired clinical samples and is suitable for application to therapeutic drug monitoring of pazopanib.

KW - clinical validation

KW - DBS

KW - pazopanib

KW - PK

KW - therapeutic drug monitoring

UR - https://www.scopus.com/pages/publications/84952683168

U2 - 10.4155/bio.15.235

DO - 10.4155/bio.15.235

M3 - Review article

C2 - 26652864

AN - SCOPUS:84952683168

SN - 1757-6180

VL - 8

SP - 123

EP - 134

JO - Bioanalysis

JF - Bioanalysis

IS - 2

ER -

Development and clinical validation of an LC-MS/MS method for the quantification of pazopanib in DBS

Abstract

Keywords

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