TY - JOUR
T1 - Method development and validation for the quantification of dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometry
AU - Lankheet, N. A.G.
AU - Hillebrand, M. J.X.
AU - Rosing, H.
AU - Schellens, J. H.M.
AU - Beijnen, J. H.
AU - Huitema, A. D.R.
PY - 2013/4/1
Y1 - 2013/4/1
N2 - To support pharmacokinetic-guided dosing in individual patients, a fast and accurate method for simultaneous determination of anticancer tyrosine kinase inhibitors (TKIs) dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma was developed using high-performance liquid chromatography and detection with tandem mass spectrometry (HPLC-MS/MS). Stable isotopically labeled compounds of the eight different TKIs were used as internal standards. Plasma proteins were precipitated and an aliquot of supernatant was directly injected onto a reversed phase chromatography system consisting of a Gemini C18 column (50×2.0mm i.d., 5.0μm particle size) and then compounds were eluted with a gradient. The outlet of the column was connected to a triple quadrupole mass spectrometer with electrospray interface. Ions were detected in the positive multiple reaction monitoring mode. This method was validated over a linear range from 20.0 to 10,000ng/mL for erlotinib, gefitinib, imatinib, lapatinib, nilotinib and sorafenib, and from 5.00 to 2500ng/mL for dasatinib and sunitinib. Results from the validation study demonstrated good intra- and inter-assay accuracy (<13.1%) and precision (10.0%) for all analytes. This method was successfully applied for routine therapeutic drug monitoring purposes in patients treated with the investigated TKIs.
AB - To support pharmacokinetic-guided dosing in individual patients, a fast and accurate method for simultaneous determination of anticancer tyrosine kinase inhibitors (TKIs) dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma was developed using high-performance liquid chromatography and detection with tandem mass spectrometry (HPLC-MS/MS). Stable isotopically labeled compounds of the eight different TKIs were used as internal standards. Plasma proteins were precipitated and an aliquot of supernatant was directly injected onto a reversed phase chromatography system consisting of a Gemini C18 column (50×2.0mm i.d., 5.0μm particle size) and then compounds were eluted with a gradient. The outlet of the column was connected to a triple quadrupole mass spectrometer with electrospray interface. Ions were detected in the positive multiple reaction monitoring mode. This method was validated over a linear range from 20.0 to 10,000ng/mL for erlotinib, gefitinib, imatinib, lapatinib, nilotinib and sorafenib, and from 5.00 to 2500ng/mL for dasatinib and sunitinib. Results from the validation study demonstrated good intra- and inter-assay accuracy (<13.1%) and precision (10.0%) for all analytes. This method was successfully applied for routine therapeutic drug monitoring purposes in patients treated with the investigated TKIs.
KW - LC-MS/MS
KW - Therapeutic drug monitoring
KW - Tyrosine kinase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84874944093&partnerID=8YFLogxK
U2 - 10.1002/bmc.2814
DO - 10.1002/bmc.2814
M3 - Article
C2 - 22987603
AN - SCOPUS:84874944093
SN - 0269-3879
VL - 27
SP - 466
EP - 476
JO - Biomedical Chromatography
JF - Biomedical Chromatography
IS - 4
ER -