PMID- 30361035
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20181211
IS  - 1873-3778 (Electronic)
IS  - 0021-9673 (Linking)
VI  - 1579
DP  - 2018 Dec 7
TI  - Coupling of salting-out assisted liquid-liquid extraction with on-line stacking 
      for the analysis of tyrosine kinase inhibitors in human plasma by capillary zone 
      electrophoresis.
PG  - 121-128
LID - S0021-9673(18)31280-9 [pii]
LID - 10.1016/j.chroma.2018.10.017 [doi]
AB  - Developing an easy to use, cheap and fast analytical methodology is highly 
      demanded for clinical practices, such as therapeutic drug monitoring (TDM). The 
      present work deals with the development of an analytical methodology for the 
      analysis of four basic anticancer drugs, namely tyrosine kinase inhibitors 
      (TKIs), in human plasma by combining salting-out assisted liquid-liquid 
      extraction (SALLE) with capillary electrophoresis (CE). This SALLE-CE methodology 
      makes a full use of the advantages of both techniques by combining extraction, 
      on-line concentration and separation in a simple way. First, plasma samples 
      containing TKIs are mixed with acetonitrile (ACN) in appropriate volumes to 
      precipitate proteins. After vortexing and centrifugation, sodium chloride (NaCl) 
      is added to the plasma-ACN mixture to induce a two phases separation. TKIs are 
      efficiently extracted (60-100% extraction efficiency) in the upper (mostly 
      organic) phase which is directly analyzed by capillary electrophoresis (CE) 
      coupled to UV detection. The high content of ACN in the upper phase allows the 
      stacking of the analytes in the capillary (on-line stacking) during analysis. For 
      the first time thanks to this electrophoretic process, the injected sample volume 
      can be as large as 80% of the capillary volume (till the detector window). Good 
      linearity was obtained for each TKI in the concentration range 60-2000 ng/ml with 
      correlation coefficient (r(2)) between 0.997 and 0.999. LOD and LOQ in human plasma 
      with such large injected volume were determined from 16 to 280 ng/ml and from 62 
      to 900 ng/ml respectively depending on the TKI. Recoveries for the four TKIs 
      ranged from 60 to 100%. The repeatability of the SALLE-CE methodology for the 
      analysis of TKIs in human plasma was evaluated with injected sample volume equal 
      to 80% of the capillary volume till detector window. Relative standard deviations 
      (RSDs) of less than 1.24 and 2.84% on migration times and corrected peak areas 
      respectively were obtained at the LOQ. The sensitivity was enhanced by 61 to 265 
      folds confirming the applicability of the proposed methodology for the assay of 
      TKIs in patients' plasma.
CI  - Copyright (c) 2018 Elsevier B.V. All rights reserved.
FAU - Ahmed, Omar S
AU  - Ahmed OS
AD  - Institut des Biomolecules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, 
      Montpellier, France.
FAU - Ladner, Yoann
AU  - Ladner Y
AD  - Institut des Biomolecules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, 
      Montpellier, France.
FAU - Montels, Jerome
AU  - Montels J
AD  - Institut des Biomolecules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, 
      Montpellier, France.
FAU - Philibert, Laurent
AU  - Philibert L
AD  - Institut regional du Cancer de Montpellier (ICM), Departement de Pharmacie et 
      Pharmacologie, Montpellier, France.
FAU - Perrin, Catherine
AU  - Perrin C
AD  - Institut des Biomolecules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, 
      Montpellier, France. Electronic address: catherine.perrin@umontpellier.fr.
LA  - eng
PT  - Journal Article
DEP - 20181015
PL  - Netherlands
TA  - J Chromatogr A
JT  - Journal of chromatography. A
JID - 9318488
RN  - 0 (Acetonitriles)
RN  - 0 (Enzyme Inhibitors)
RN  - 451W47IQ8X (Sodium Chloride)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - Z072SB282N (acetonitrile)
SB  - IM
MH  - Acetonitriles/chemistry
MH  - Blood Chemical Analysis/*methods
MH  - Centrifugation
MH  - *Electrophoresis, Capillary
MH  - Enzyme Inhibitors/*blood/metabolism
MH  - Humans
MH  - *Liquid-Liquid Extraction
MH  - Plasma/chemistry
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Sodium Chloride/*chemistry
OTO - NOTNLM
OT  - Capillary electrophoresis
OT  - On-line CE stacking
OT  - Salting-out assisted liquid-liquid extraction (SALLE)
OT  - Tyrosine Kinase Inhibitor (TKI)
EDAT- 2018/10/27 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/10/27 06:00
PHST- 2018/07/02 00:00 [received]
PHST- 2018/10/03 00:00 [revised]
PHST- 2018/10/13 00:00 [accepted]
PHST- 2018/10/27 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/10/27 06:00 [entrez]
AID - S0021-9673(18)31280-9 [pii]
AID - 10.1016/j.chroma.2018.10.017 [doi]
PST - ppublish
SO  - J Chromatogr A. 2018 Dec 7;1579:121-128. doi: 10.1016/j.chroma.2018.10.017. Epub 
      2018 Oct 15.