Biomedical Engineering Reference
In-Depth Information
5 mg/kg. Sinapinic acid (SA) matrix was used. The tissue section samples were
analyzed by MALDI-TOF-MS/MS. The parent compound (
m/z
394, [M+H]
+
) was
detected in all tissues analyzed. The metabolites (
m/z
380, [M+H]
+
) following
drug
O
-dealkylation could also be detected in liver sections. MS imaging experi-
ments using MALDI in MS/MS mode allowed visualizing the distribution of
the parent compound in liver and spleen tissues. By calculating the ratio between
the total ion intensities of MS images for liver and spleen sections, a value of 6:1
was found, which was in good agreement with the quantitative data obtained by
LC-MS/MS analysis.
4.1.3
Kidney-Liver-Brain
Cornett [
60
] reported images for olanzapine (OLZ) in kidney and liver and Imatinib
in glioma/mouse brain by MSI. OLZ was administered p.o. at dose of 8 mg/kg to
10 week-old male Fischer 344 rats. Animals were euthanized at 2 h postdose.
Three milligrams of Imatinib in 100 mL of PBS was administered by esophageal
gavage to a mouse with 14-day old tumor. Tissue sections (12 mm thick) were cut
on a cryostat, thaw mounted onto gold-plated stainless-steel plates. A matrix
solution of HCCA at 10 mg/mL was prepared in water/acetonitrile (1:1). Arrays of
matrix microdroplets were applied onto tissue sections using a Portrait 630
(Labcyte Inc., Sunnyvale CA). Four major ions observed at the nominal
m/z
of the
2-hydroxymethyl metabolite of OLZ were detected within a range of 200 mDa in
each tissue.
Bouslimani [
153
] studied oxaliplatin in rat kidney. Frozen kidney tissue sections
of 15 mm thickness were coated using 10 mg/mL CHCA in ACN-0.1%TFA (50:50,
vol/vol) either manually or using an Airbrush sprayer. The MALDI imaging was
performed using a MALDI-TOF/TOF analyzer. Oxaliplatin in kidney tissues was
detected after incubation under HIPEC conditions. This experiment confirmed that
oxaliplatin and its metabolites, monocysteine and monomethionine complexes were
located at the cortex with weak penetration inside kidney (0.2-0.5 mm).
4.1.4
Skin
Bunch et al. [
154
] first reported using MALDI-MS to examine the absorption and
image the distribution of antifungal agent into skin. A porcine epidermal tissue was
treated with a medicated shampoo containing ketoconazole as active ingredient.
Following incubation for 1 h at 37 °C all excess formulation was washed from the
surface. Due to poor matrix coverage from application methods, a cross section of
the drug-treated tissue was blotted onto a cellulose membrane that was precoated
with matrix CHCA by airspray deposition. The MS image by MALDI showed that
the ketoconazole penetrated into the skin only as far as the dermis with no absorption
into the underlying connective tissue
