A quantitation method for mass spectrometry imaging.
A new quantitation method for mass spectrometry imaging (MSI) with matrix-assisted laser desorption/ionization (MALDI) has been developed. In this method, drug concentrations were determined by tissue homogenization of five 10 µm tissue sections adjacent to those analyzed by MSI. Drug levels in tissue extracts were measured by liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The integrated MSI response was correlated to the LC/MS/MS drug concentrations to determine the amount of drug detected per MSI ion count. The study reported here evaluates olanzapine in liver tissue. Tissue samples containing a range of concentrations were created from liver harvested from rats administered a single dose of olanzapine at 0, 1, 4, 8, 16, 30, or 100 mg/kg. The liver samples were then analyzed by MALDI-MSI and LC/MS/MS. The MALDI-MSI and LC/MS/MS correlation was determined for tissue concentrations of ~300 to 60,000 ng/g and yielded a linear relationship over two orders of magnitude (R(2) = 0.9792). From this correlation, a conversion factor of 6.3 ± 0.23 fg/ion count was used to quantitate MSI responses at the pixel level (100 µm). The details of the method, its importance in pharmaceutical analysis, and the considerations necessary when implementing it are presented.
Advanced Technology, GPRD, Abbott Laboratories, Abbott Park, IL 60064, USA. stormy.koeniger@abbott.com
Stormy L
SL
Koeniger
Nari
N
Talaty
Yanping
Y
Luo
Damien
D
Ready
Martin
M
Voorbach
Terese
T
Seifert
Steve
S
Cepa
Jane A
JA
Fagerland
Jennifer
J
Bouska
Wayne
W
Buck
Robert W
RW
Johnson
Stephen
S
Spanton
D000818:Animals; D001569:Benzodiazepines / Q000008:administration & dosage / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D006651:Histocytochemistry / Q000379:methods*; D016014:Linear Models; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D000077152:Olanzapine; D051381:Rats; D017207:Rats, Sprague-Dawley; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
D001569:Benzodiazepines; D000077152:Olanzapine