Biomedical Engineering Reference
In-Depth Information
Bosutinib
50
530.0
113.1
141.1
0
RT:4.15
100
Erlotinib
50
394.2
278.1
0
RT:4.12
100
Erlotinib-D
5
50
400.0
278.1
0
RT:3.11
100
Gefitinib
50
447.1
128.2
0
RT:3.11
100
Gefitinib-D
3
50
452.3
128.2
0
RT:7.23
100
Sorafenib
13
CD
3
50
469.1
256.1
255.1
0
RT:7.34
100
PLX4032
50
490.2
255.1
383.1
0
100
RT:2.69
Imatinib-D
8
503.2
394.2
50
0
0
1
2
3
4
Time (min)
5
6
7
8
9
Fig. 1
A multiplex LC tandem MS for the quantification of the targeted anticancer agents bosutinib,
gefitinib, erlotinib, and vemurafenib (formerly PLX4032). The chromatographic profile of a QC
control containing 37.5 ng/ml of bosutinib, 375 ng/ml of gefitinib and erlotinib, and 3,000 ng/ml of
vemurafenib is shown. Chromatographic separations were performed on a column Waters XTerra MS
C18 2.1 × 50 mm. Solvent A consisted of 10 mM ammonium acetate containing 1.5 % formic acid (pH
2.3). Solvent B was acetonitrile with 1 % formic acid. The mobile phase was delivered at 0.3 ml/min
according to the gradient elution program: 0-9 min, solvent B 5 % → 85 % B, followed by a re-
equilibration step. Quantifications were done using the internal standards erlotinib-D
6
and ge fi tinib-D
3
.
The internal standards (I.S.) imatinib-D
8
and sorafenib-
13
C-D
3
have similar retention times as bosu-
tinib and verumafenib, respectively, and were used as I.S. for these latter drugs, because of the lack of
labeled standards at the time the assay was developed. On the same chromatographic profiles are
shown in offset the superimposed ionization traces of the selected transitions during the analysis of six
blank plasma extracts with post-column infusion of a solution containing the four TKIs (1 m g/ml)
