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Quantitation of unbound sunitinib and its metabolite N ‐desethyl sunitinib (SU12662) in human plasma by equilibrium dialysis and liquid chromatography–tandem mass spectrometry: application to a pharmacokinetic study
Author(s) -
Rais Rana,
Zhao Ming,
He Ping,
Xu Linping,
Deeken John F.,
Rudek Michelle A.
Publication year - 2012
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2697
Subject(s) - chemistry , chromatography , metabolite , sunitinib , liquid chromatography–mass spectrometry , formic acid , selected reaction monitoring , tandem mass spectrometry , pharmacokinetics , bioanalysis , analyte , mass spectrometry , active metabolite , extraction (chemistry) , pharmacology , medicine , biochemistry , renal cell carcinoma , oncology
A rapid, selective, and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous determination of unbound sunitinib and its active metabolite N ‐desethyl sunitinib in plasma. Plasma and post‐dialysis buffer samples were extracted using a liquid–liquid extraction procedure with acetonitrile– n ‐butylchloride (1:4, v/v). Chromatographic separation was achieved on a Waters X‐Terra® MS RP 18 column with a mobile phase consisting of acetonitrile and water (60:40, v/v) containing formic acid (0.1%, v/v) using an isocratic run, at a flow‐rate of 0.2 mL/min. Analytes were detected by electrospray tandem mass spectrometry in the selective reaction monitoring mode. Linear calibration curves were generated over the ranges 0.1–100 and 0.02–5 ng/mL for sunitinib and 0.2–200 and 0.04–10 ng/mL for N ‐desethyl sunitinib in plasma and in phosphate‐buffered solution, respectively. The values for both within‐day and between‐day precision and accuracy were well within the generally accepted criteria for analytical methods. The analytical range was sufficient to determine the unbound and total concentrations of both analytes. The method was applied for measurement unbound concentrations in addition to total concentrations of sunitinib and its metabolite in plasma of a cancer patient receiving 50 mg daily dose. Copyright © 2012 John Wiley & Sons, Ltd.