Imaging Mass Spectrometry of Intact Biomolecules in Tissue Sections - Proteomic and Metabolomic Approaches to Biomarker Discovery - page 389

of creatine and the increased presence of lyso-
phospholipids in the damaged tissue. Lysophos-
pholipids LPC 16:0 [M

arachidonic acid in an effort to protect against
ischemic cell death.

H] þ ( m/z 496), LPC 16:0

þ

Na] þ ( m/z 518), LPC 18:0 [M H] þ or

[M

þ þ

DRUG ANALYSIS

unidenti ed LPE ( m/z 524), LCP 18:1 [M

þ

Na] þ or LPC 20:4 [M H] þ ( m/z 544) and LPC

þ

Na] þ ( m/z 546) were found to be at

18:0 [M Imagingmass spectrometryhas been employed

in the pharmaceutical industry for determination
of the spatial distribution and quantitation of
drugs and their metabolites in tissue sections. 66 e 68
Traditional drug analyses have been carried out
using quantitative whole body autoradiography
that allows for the visualization of radiolabeled
compounds throughout thin sections of dosed
animals. 69 However, this technology shows only
the location of the label and does not identify the
compound (parent drug or metabolite). Alterna-
tively, LC-MS-based approaches can easily distin-
guish different metabolites but spatial localization
is lost due to the homogenization of the tissue prior
to analysis. IMS is ideal for this purpose because it

þ

signi cantly greater levels in the infarcted tissue

than in the surrounding unaffected tissue.
Conversely, intact phospholipids PC (18:0/

Na] þ ( m/z 832) and PC (18:0/20:4) 20:4) [M þ

K] þ ( m/z 848) were found to be in high
abundance in the normal tissue but absent
from the infarcted tissue ( Figure 3 ). The presence
of increased levels of lysophospholipids along
with decreased levels of intact lipids indicated
increased activity of phospholipase A 2 , which
hydrolyzes the SN-2 acyl bond of intact phos-
pholipids, within the infarcted tissue area. This

[M þ

finding is in accordance with previous reports 65
that phospholipase A 2 acts on lipids containing

FIGURE 3 MS images

for the

(A) (B)

[M K] þ of LPE 18:0 at m/z 520 (A),

the [M

þ

Na] þ of LPC 18:0 at m/z 546
(B), the [M

þ

Na] þ of LPC 16:0 at m/z
518 (C), and the [M

þ

K] þ of PC
(18:0/20:4) at m/z 848 (D) from a heart
following [left anterior descending]
coronary artery ligation. All images
were generated by plotting the ion
intensity divided by the TIC. (Re-
printed with permission from reference
#64. Copyright 2012 American Chemical
Society.)

þ

(C) (D)