Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues.
Ambient ionization methods for MS enable direct, high-throughput measurements of samples in the open air. Here, we report on one such method, desorption electrospray ionization (DESI), which is coupled to a linear ion trap mass spectrometer and used to record the spatial intensity distribution of a drug directly from histological sections of brain, lung, kidney, and testis without prior chemical treatment. DESI imaging provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measuring the abundance of the intact ion at m/z 327.1, and ii) monitoring the dissociation of the protonated drug compound at m/z 327.1 to its dominant product ion at m/z 270.1. In lung tissues, DESI imaging was performed in the full-scan mode over an m/z range of 200-1100, providing an opportunity for relative quantitation by using an endogenous lipid to normalize the signal response of clozapine. The presence of clozapine was detected in all tissue types, whereas the presence of the N-desmethyl metabolite was detected only in the lung sections. Quantitation of clozapine from the brain, lung, kidney, and testis, by using LC-MS/MS, revealed concentrations ranging from 0.05 microg/g (brain) to a high of 10.6 microg/g (lung). Comparisons of the results recorded by DESI with those by LC-MS/MS show good agreement and are favorable for the use of DESI imaging in drug and metabolite detection directly from biological tissues.
Wiseman
Justin M
JM
Prosolia, Inc., Indianapolis, IN 46202, USA.
Ifa
Demian R
DR
Zhu
Yongxin
Y
Kissinger
Candice B
CB
Manicke
Nicholas E
NE
Kissinger
Peter T
PT
Cooks
R Graham
RG
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D003024:Clozapine / Q000493:pharmacokinetics*; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D003024:Clozapine