title: Evaluation of an accurate mass approach for the simultaneous detection of drug and metabolite distributions via whole-body mass spectrometric imaging.
abstract: In drug discovery and development, in vitro absorption and metabolism assays along with in vivo pharmacokinetic (PK), pharmacodynamic (PD), and toxicokinetic (TK) studies are used to evaluate a potential drug candidate. More recently, imaging mass spectrometry approaches have been successfully reported to aid in the preclinical assessment of drug candidates, resulting in the rapid and noteworthy acceptance of the technique in pharmaceutical research. Traditionally, drug distribution studies via mass spectrometric imaging (MSI) are performed as targeted MS/MS analyses, where the analytes of interest, drug and/or metabolite, are known before the imaging experiment is performed. The study presented here describes a whole-body mass spectrometric imaging (WB-MSI) approach using a hybrid MALDI-LTQ-Orbitrap-MS to detect the distribution of reserpine at 2 h post a 20 mg/kg oral dose. This study effectively demonstrates the utility of obtaining accurate mass measurements across a wide mass range combined with postprocessing tools to efficiently identify drug and metabolite distributions without the need for any a priori knowledge.
authors: Genentech, Inc., South San Francisco, California 94080, USA. sheerink@gene.com
authors: Sheerin K
authors: SK
authors: Shahidi-Latham
authors: Sucharita M
authors: SM
authors: Dutta
authors: Maria C
authors: MC
authors: Prieto Conaway
authors: Patrick J
authors: PJ
authors: Rudewicz
mesh_terms: D000818:Animals; D008297:Male; D057054:Molecular Imaging / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000378:metabolism* / Q000493:pharmacokinetics; D013997:Time Factors; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D012110:Reserpine