Biomedical Engineering Reference
In-Depth Information
Table 4
Molecular masses and SRM transitions for tamoxifen and some of its metabolites of interest
Precursor
ion
a
[M + H]
+
Molecular
weight
Analytes
Abbreviation
Production
Tamoxifen
Tam
371
372
72
N
-Desmethyl-tamoxifen
N
-D-Tam
357
358
58
N
,
N
-Didesmethyl-tamoxifen
N
-D-D-Tam
343
344
44
4-Hydroxy-tamoxifen
4-OH-Tam
387
388
72
3-Hydroxy-tamoxifen
3-OH-Tam
387
388
72
4 ¢ -Hydroxy-tamoxifen
4 ¢ -OH-Tam
387
388
72
a -Hydroxy-tamoxifen
a -OH-Tam
387
388
72
Tamoxifen-
N
-oxide
Tam-NO
387
388
72
4-Hydroxy-
N
-desmethyl-tamoxifen
Endoxifen
373
374
58
3-Hydroxy-
N
-desmethyl-tamoxifen
3-OH-
N
-D-Tam
373
374
58
4 ¢ -Hydroxy-
N
-desmethyl-tamoxifen
4 ¢ -OH-
N
-D-Tam
373
374
58
a -Hydroxy-
N
-desmethyl-tamoxifen
a - OH-
N
-D-Tam
373
374
58
Tamoxifen-
N
+
-glucuronide
Tam-
N
+
-Gluc
548
548
372
Tamoxifen-4-
O
-glucuronide
Tam-4-
O
-Gluc
563
564
388
Tamoxifen-3-
O
-glucuronide
Tam-3-
O
-Gluc
563
564
388
N
-Desmethyl-tamoxifen-4-
O
-
glucuronide
N
-D-Tam-4-
O
-Gluc
549
550
374
N
-Desmethyl-tamoxifen-3-
O
-
glucuronide
N
-D-Tam-3-
O
-Gluc
549
550
374
a
Molecule protonation occurs on the amino group
Another drawback, challenging the routine applicability of some of these
LC-MS and LC-MS/MS assays for measuring exposure to tamoxifen and its active
metabolites is that for some assays no data have been provided concerning the
validation process. Other methods have only been partially validated and have not
or limitedly addressed matrix effects (ME) issues.
3.4
Handling Matrix Effects
Matrix effects (ME), caused by co-eluting endogenous and exogenous matrix compo-
nents, significantly affect the efficiency and reproducibility of the ionization process
of target analytes. This phenomenon represents a major concern for LC-MS bioana-
lytical method precision, accuracy, sensitivity, and robustness. Amongst the atmospheric
pressure ionization interfaces used in LC-MS systems, ESI source is more prone to
signal alteration (ion suppression or enhancement) due to matrix. Therefore, careful
evaluation and correction for ME must be considered particularly with ESI-MS.
The use of stable isotope labeled (SIL) version of the target analyte as an internal
standard (IS) is theoretically considered to be the best approach to compensate or
correct for matrix effects and minimize their influence on the accuracy and preci-
sion of ESI-MS quantitative assays.
