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LAAN-A-LM-E114

Application Liquid Chromatograph Mass Spectrometry

News
Simultaneous Analysis of Tyrosine Kinase Inhibitors
in Human Blood Plasma with LC/MS/MS
No. C143

Cancer treatment in recent years employs drugs known second and third generation drugs, continue to be
as molecular targeted drugs that were developed to developed.
target molecules related to the growth, invasion, and This article introduces an example of simultaneous
metastasis of tumor cells in order to inhibit tumor cell analysis of EGFR-TKIs, ALK-TKIs, and metabolites in
growth. human blood plasma for the purpose of research into
Lung cancer treatment employs tyrosine kinase pharmacokinetics using the triple quadrupole high
inhibitors (TKIs), which target the epidermal growth performance liquid chromatograph mass spectrometer
factor receptor (EGFR) and anaplastic lymphoma kinase LCMS-8050.
(ALK), and new molecular targeted drugs, referred to as T. Tsukamoto

„ Simultaneous Analysis of Four EGFR-TKIs and Three ALK-TKIs
Samples with the standard EGFR-TKIs and ALK-TKIs for analysis. MRM measurement with LC/MS/MS can
listed in Table 1 added to a control human blood selectively detect target drugs according to their
plasma were deproteinized according to the process in molecular mass and structure (Fig. 2 and Fig. 3).
Fig. 1 and the resulting supernatants were submitted

Table 1 EGFR-TKIs, ALK-TKIs, and Metabolites
Molecular Monoisotopic MRM transition
Compound
formula mass [u] m/z
Afatinib C24H25ClFN5O3 485.163 486.2 > 371.1
Erlotinib C22H23N3O4 393.169 394.2 > 278.1
OSI-420 C21H21N3O4 379.153 380.2 > 278.1
*1
EGFR-TKIs
Gefitinib C22H24ClFN4O3 446.152 447.2 > 128.1
Osimertinib C28H33N7O2 499.270 500.3 > 72.1
AZ5104 C27H31N7O2 485.254 486.3 > 72.2
*2
Alectinib C30H34N4O2 482.268 483.3 > 396.3
ALK-TKIs Crizotinib C21H22Cl2FN5O 449.119 450.1 > 260.2
Ceritinib C28H36ClN5O3S 557.223 558.2 > 433.1
Pretreatment Workflow of Blood *1 Erlotinib metabolite, *2 Osimertinib metabolite
Plasma Samples

Precursor Ion and Product Ion of
Erlotinib

Mass Chromatograms of Human Blood Plasma Samples with Standard Additives