naa a22 4500 510738265 CHVBK 20180411083018.0 cr unu---uuuuu 180411e20130301xx s 000 0 eng 10.1007/s12127-012-0113-1 doi (NATIONALLICENCE)springer-10.1007/s12127-012-0113-1 Resolving the microcosmos of complex samples: UPLC/travelling wave ion mobility separation high resolution mass spectrometry for the analysis of in vivo drug metabolism studies [Elektronische Daten] [Stefan Blech, Ralf Laux] In vivo drug metabolism studies with low concentrations of analytes and high matrix burden are challenging. Of special interest are ‘first-in-man' studies in early stages of pharmaceutical development that do not use 14C labeled drug candidates. Beside conventional MS-fishing techniques which are biased towards known/expected metabolites and mass defect filtration procedures, this paper focuses on the untargeted/unbiased analysis of drug related compounds in complex matrices using two orthogonal separation techniques: UPLC and TWIMS. Standard sample material after oral administration of a drug compound to rats was investigated by UPLC/TWIMS in MSE acquisition mode using interlaced collision energies for the parallel detection of [M+H]+ parent ions and fragments. Due to the fragmentation after ion mobility separation in the transfer region of the Synapt G2-triwave device, [M+H]+ ion species are aligned with their related fragments by virtue of possessing the same retention time and drift time profile. Four dimensional data analysis of the continuum raw data was performed by automated peak picking and alignment within the MSE viewer software. As result, completely purified MS- and MS/MS-data of metabolites were extracted from raw mass data with high matrix burden and were used without compromise for structure elucidation. This analytical methodology is universally applicable for the unbiased/untargeted and robust analysis of any analyte of interest in complex matrices, including small molecules, peptides and proteins. The high quality data files can be used as data repositories for the purpose of retrospective analysis which is of particular interest for the long term process in drug development. The Author(s), 2012 Drug metabolism nationallicence Complex sample material nationallicence Ion mobility separation nationallicence 4D-data analysis nationallicence Data repository nationallicence MSE-analysis nationallicence Blech Stefan Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co KG, 88397, Biberach, Germany aut Laux Ralf Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co KG, 88397, Biberach, Germany aut International Journal for Ion Mobility Spectrometry Springer-Verlag 16/1(2013-03-01), 5-17 1435-6163 16:1<5 2013 16 12127 https://doi.org/10.1007/s12127-012-0113-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12127-012-0113-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Blech Stefan Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co KG, 88397, Biberach, Germany aut NATIONALLICENCE 700 1- Laux Ralf Department of Drug Metabolism and Pharmacokinetics, Boehringer Ingelheim Pharma GmbH & Co KG, 88397, Biberach, Germany aut NATIONALLICENCE 773 0- International Journal for Ion Mobility Spectrometry Springer-Verlag 16/1(2013-03-01), 5-17 1435-6163 16:1<5 2013 16 12127 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer