Detection of chemical warfare agent simulants and hydrolysis products in biological samples by paper spray mass spectrometry.
Paper spray ionization coupled to a high resolution tandem mass spectrometer (a quadrupole orbitrap) was used to identify and quantitate chemical warfare agent (CWA) simulants and their hydrolysis products in blood and urine. Three CWA simulants, dimethyl methylphosphonate (DMMP), trimethyl phosphate (TMP), and diisopropyl methylphosphonate (DIMP), and their isotopically labeled standards were analyzed in human whole blood and urine. Calibration curves were generated and tested with continuing calibration verification standards. Limits of detection for these three compounds were in the low ng mL-1range for the direct analysis of both blood and urine samples. Five CWA hydrolysis products, ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), isobutyl methylphosphonic acid (iBuMPA), cyclohexyl methylphosphonic acid (CHMPA), and pinacolyl methylphosphonic acid (PinMPA), were also analyzed. Calibration curves were generated in both positive and negative ion modes. Limits of detection in the negative ion mode ranged from 0.36 ng mL-1to 1.25 ng mL-1in both blood and urine for the hydrolysis products. These levels were well below those found in victims of the Tokyo subway attack of 2 to 135 ng mL-1. Improved stability and robustness of the paper spray technique in the negative ion mode was achieved by the addition of chlorinated solvents. These applications demonstrate that paper spray mass spectrometry (PS-MS) can be used for rapid, sample preparation-free detection of chemical warfare agents and their hydrolysis products at physiologically relevant concentrations in biological samples.
Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA. nmanicke@iupui.edu.
Josiah
J
McKenna
Elizabeth S
ES
Dhummakupt
Theresa
T
Connell
Paul S
PS
Demond
Dennis B
DB
Miller
J
J
Michael Nilles
Nicholas E
NE
Manicke
Trevor
T
Glaros
D002619:Chemical Warfare Agents / Q000032:analysis*; D006801:Humans; D006868:Hydrolysis; D013058:Mass Spectrometry; D009943:Organophosphorus Compounds / Q000097:blood* / Q000652:urine*; D010209:Paper
D002619:Chemical Warfare Agents; D009943:Organophosphorus Compounds