475 ISSN: 1469-0667 © IM Publications LLP 2013 doi: 10.1255/ejms.1254 All rights reserved EUROPEAN JOURNAL OF MASS SPECTROMETRY Impact of drug administration route on drug delivery and distribution into the lung: an imaging mass spectrometry approach Riccardo Zecchi, a Marcello Trevisani, b Maria Pittelli, b Pamela Pedretti, b Maria Elena Manni, b Giuseppe Pieraccini, a Barbara Pioselli, c Francesco Amadei, c Gloriano Moneti a and Silvia Catinella c a Centro di servizi di spettrometria di massa (CISM), University of Florence, Italy b Chiesi Farmaceutici SpA, Corporate Preclinical R&D–FABER Project Group, Florence, Italy c Chiesi Farmaceutici SpA, Corporate Preclinical R&D–Analytics and Early Formulations Department, Parma, Italy During the last decade, significant technological improvements in mass spectrometry have had a great impact on drug discovery. The development of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) has set a new frontier for the study of the distribution of endogenous and exogenous molecules present within a tissue. MALDI-IMS is a surface sampling technique that allows not only the detection of multiple analytes but also gives the spatial distribution of those analytes. Active compounds for pulmonary disease need an optimal and well-studied delivery into the lungs, in order to assure distribution with greater penetration into the peripheral or the alveolar region of the lung to maximize the therapeutic effects. IMS is very useful in the field of drug discovery, showing drug delivery and distribution in the body and organs. In this study, we present a comparison between two different ways of carrying out pulmonary drug administration: inhalation of a nebulized aerosol of aqueous drug solutions and intratracheal administration, which is much simpler, not expensive and commonly used during in vivo screening. Tiotropium bromide is a long-acting anticholinergic medicine used for maintenance treatment of chronic obstructive pulmonary disease. In the present work, tiotropium was administered by nebulization and by intratracheal instillation to guinea pigs at doses able to induce significant anti-bronchoconstrictive activity. Lung samples were dissected, frozen, cryosectioned and coated with matrix (a-hydroxy-cinnamic acid). IMS analyses were performed using a MALDI-LTQ-Orbitrap XL. Using this technique we were able to compare different distributions of the drug depending on the method of administration. Keywords: MALDI-IMS, tiotropium, COPD, nebulized aerosol, intratracheal administration Introduction Mass spectrometry (MS) is a powerful technique capable of detecting and measuring a wide range of organic compounds and is commonly used in the field of biology for qualitative and quantitative purposes. 1 The versatility of the technique and continuous innovation progress on ionization sources permit the processing of a large variety of analytes in different matrices, from volatile compounds to biological fluids or solid samples. Matrix-assisted laser desorption/ ionization imaging mass spectrometry (MALDI-IMS) is a promising technique that allows the direct analysis of solid biological samples such as tissue sections. 2–4 The possibility of detecting and localizing both endogenous (metabolites, lipids or proteins) and exogenous compounds (drugs and their metabolites) is very important for biological research, R. Zecchi et al., Eur. J. Mass Spectrom. 19, 475–482 (2013) Received: 16 May 2013 n Accepted: 10 October 2013 n Publication: 30 December 2013 7 th Italian Mass Spectrometry PharmaDay