Header

UZH-Logo

Maintenance Infos

LC QTOF with SWATH acquisition: Systematic studies on its use for screenings in clinical and forensic toxicology and comparison with IDA and targeted MRM approaches


Roemmelt, Andreas T; Steuer, Andrea E; Poetzsch, Michael; Kraemer, Thomas (2014). LC QTOF with SWATH acquisition: Systematic studies on its use for screenings in clinical and forensic toxicology and comparison with IDA and targeted MRM approaches. Analytical Chemistry, 86(23):11742-11749.

Abstract

Forensic and clinical toxicological screening procedures are more and more employing LC-MS/MS techniques with information dependent acquisition (IDA) approaches. It is known that complexity of sample and settings of IDA might prevent important compounds from being triggered. Therefore, data independent acquisition methods (DIA) should be more suitable for systematic toxicological analysis (STA). The DIA method sequential window acquisition of all theoretical fragment-ion spectra (SWATH) which uses Q1 windows of 20-35 Da for data independent fragmentation, was systematically investigated for its suitability for STA. Quality of SWATH generated mass spectra were evaluated with regard to mass error, relative abundance of the fragments and library hits. With the Q1 window set to 20-25 Da, several precursors pass Q1 at the same time and are fragmented thus impairing the library search algorithms to a different extent: forward fit was less affected than reverse fit and purity fit. Mass error was not affected. Relative abundance of the fragments was concentration dependent for some analytes and was influenced by co-fragmentation, especially of deuterated analogues. Also the detection rate of IDA compared to SWATH was investigated in a forced coelution experiment (up to 20 analytes coeluting). Even using several different IDA settings it was observed that IDA failed to trigger relevant compounds. Screening results of 382 authentic forensic cases revealed that SWATH’s detection rate was superior to IDA, which failed to trigger about 10% of the analytes.

Abstract

Forensic and clinical toxicological screening procedures are more and more employing LC-MS/MS techniques with information dependent acquisition (IDA) approaches. It is known that complexity of sample and settings of IDA might prevent important compounds from being triggered. Therefore, data independent acquisition methods (DIA) should be more suitable for systematic toxicological analysis (STA). The DIA method sequential window acquisition of all theoretical fragment-ion spectra (SWATH) which uses Q1 windows of 20-35 Da for data independent fragmentation, was systematically investigated for its suitability for STA. Quality of SWATH generated mass spectra were evaluated with regard to mass error, relative abundance of the fragments and library hits. With the Q1 window set to 20-25 Da, several precursors pass Q1 at the same time and are fragmented thus impairing the library search algorithms to a different extent: forward fit was less affected than reverse fit and purity fit. Mass error was not affected. Relative abundance of the fragments was concentration dependent for some analytes and was influenced by co-fragmentation, especially of deuterated analogues. Also the detection rate of IDA compared to SWATH was investigated in a forced coelution experiment (up to 20 analytes coeluting). Even using several different IDA settings it was observed that IDA failed to trigger relevant compounds. Screening results of 382 authentic forensic cases revealed that SWATH’s detection rate was superior to IDA, which failed to trigger about 10% of the analytes.

Statistics

Citations

40 citations in Web of Science®
40 citations in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Legal Medicine
Dewey Decimal Classification:340 Law
610 Medicine & health
Language:English
Date:2014
Deposited On:04 Nov 2014 12:19
Last Modified:08 Dec 2017 07:50
Publisher:American Chemical Society
ISSN:0003-2700
Publisher DOI:https://doi.org/10.1021/ac503144p

Download

Full text not available from this repository.
View at publisher