Real-time trace detection and identification of chemical warfare agent simulants using recent advances in proton transfer reaction time-of-flight mass spectrometry Fredrik Petersson 1 , Philipp Sulzer 2 , Chris A. Mayhew 3 * , Peter Watts 3 , Alfons Jordan 2 , Lukas Ma ¨rk 2 and Tilmann D. Ma ¨rk 1,2 1 Institut fu ¨r Ionenphysik und Angewandte Physik, Leopold Franzens Universita ¨t Innsbruck, Technikerstr. 25, A-6020 Innsbruck, Austria 2 Ionicon Analytik GmbH, Technikerstr. 21a, A-6020 Innsbruck, Austria 3 School of Physics and Astronomy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK Received 15 September 2009; Revised 8 October 2009; Accepted 10 October 2009 This work demonstrates for the first time the potential of using recent developments in proton transfer reaction mass spectrometry for the rapid detection and identification of chemical warfare agents (CWAs) in real-time. A high-resolution (m/Dm up to 8000) and high-sensitivity (50 cps/ppbv) proton transfer reaction time-of-flight mass spectrometer (PTR-TOF 8000 from Ionicon Analytik GmBH) has been successfully used to detect a number of CWA simulants at room temperature; namely dimethyl methylphosphonate, diethyl methylphosphonate, diisopropyl methylphospho- nate, dipropylene glycol monomethyl ether and 2-chloroethyl ethyl sulfide. Importantly, we demon- strate in this paper the potential to identify CWAs with a high level of confidence in complex chemical environments, where multiple threat agents and interferents could also be present in trace amounts, thereby reducing the risk of false positives. Instantaneous detection and identification of trace quantities of chemical threats using proton transfer reaction mass spectrometry could form the basis for a timely warning system capability with greater precision and accuracy than is currently provided by existing analytical technologies. Copyright # 2009 John Wiley & Sons, Ltd. There is an increasing need for the reliable, real-time and sensitive detection of a wide range of substances that are a threat to national security. Of the threat agents available to terrorists, chemical warfare agents (CWAs) and weaponi- sable toxic industrial chemicals are distinct in that they are not destructive to property, but will target people with the purpose of killing, injuring, incapacitating or panicking them. Three main scenarios for the detection of such chemicals may be considered. One is to detect the agents when they are produced in illegal chemical laboratories. A second is to detect them before deployment – such as looking for trace quantities on hands or objects. The third is to quickly identify the chemical agent once it is deployed, a situation requiring accurate identification which is vital not only for the protection of first responders, but also to provide rapid and effective treatment to any casualties in order to minimise fatalities. Commonly deployed equipment used for the detection of CWAs is based on ion mobility spectrometry (IMS). 1–5 IMS is a separation method, widely used in forensic, military and security applications. 6,7 Despite its success, IMS has a number of limitations, which result in the technology not being fully exploited. Its major limitation is associated with its low chemical specificity as a result of its low temporal resolution associated with the separation of mobility peaks. This not only restricts the type of compounds which can be readily detected, but it can also lead to false positives resulting from the mistaken identification of harmless interferents. In order to detect traces of CWAs with a high level of confidence in the atmosphere, adhered to people or objects or for rapid identification while retaining high sensitivity needed, a new approach is required. The recent development of a high mass resolution and high sensitivity proton transfer reaction time-of-flight mass spectrometer, PTR-TOF 8000 (Ionicon Analytik, Innsbruck, Austria), holds such a promise. 8–10 We recently highlighted the use of two PTR-TOF variants (PTR-TOF 8000 and PTR- TOF 2000) for the detection of traces of solid explosives. 11 In this short communication we present the first proof-of- principle PTR-TOF 8000 mass spectrometric measurements for the potential detection of CWAs from the volatile organic compounds (VOCs) that they emit at room temperatures. The first reported use of proton transfer reaction time-of- flight mass spectrometry (PTR-ToF-MS) for analytical purposes was by Blake et al. in 2004. 12 Subsequently, a number of other papers have been published illustrating the successful use of PTR-ToF-MS instruments for analytical purposes. 13–15 Crucially, however, the PTR-TOF 8000 instrument used in this study surpasses any of the other instruments referred to in the above papers in terms of its sensitivity and selectivity, with high mass resolution (up to 8000 m/Dm) and low detection limit (as low as a few pptv). 8–10 RAPID COMMUNICATIONS IN MASS SPECTROMETRY Rapid Commun. Mass Spectrom. 2009; 23: 3875–3880 Published online in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/rcm.4334 *Correspondence to: C. A. Mayhew, School of Physics and Astron- omy, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK. E-mail: c.mayhew@bham.ac.uk Copyright # 2009 John Wiley & Sons, Ltd.