Abstract
Clandestine bomb-makers are exposed to significant amounts of explosives and allied materials. As with any ingested xenobiotic substance, these compounds are subject to biotransformation. As such, the potential exists that characteristic suites of biomarkers may be produced and deposited in matrices that can be exploited for forensic and investigative purposes. However, before such assays can be developed, foundational data must be gathered regarding the toxicokinetics, fate, and transport of the resulting biomarkers within the body and in matrices such as urine, hair, nails, sweat, feces, and saliva. This report presents an in vitro method for simulation of human metabolic transformations using human liver microsomes and an assay applicable to representative nitro-explosives. Control and metabolized samples of TNT, RDX, HMX, and tetryl were analyzed using high-performance liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) and biomarkers identified for each. The challenges associated with this method arise from solubility issues and limitations imposed by instrumentation, specifically, modes of ionization.
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Abbreviations
- MRM:
-
multiple-reaction monitoring
- K ow :
-
octanol/water partition coefficient
- 4-ADNT:
-
4-amino-2,6-dinitrotoluene
- VP:
-
vapor pressure
- HLMs:
-
human liver microsomes
References
Gaurav D, Malik AK, Rai PK (2007) Crit Rev Anal Chem 37:227
Nambayah M, Quickenden TI (2004) Talanta 63:461
Pumera M (2008) Electrophoresis 29:269
Schulte-Ladbeck R, Vogel M, Karst U (2006) Anal Bioanal Chem 386:559
Tagliaro F, Bortolotti F (2008) Electrophoresis 29:260
Wang J (2007) Electroanalysis 19:415
de Oliveira CDR, Roehsig M, de Almeida RM et al (2007) Curr Pharm Anal 3:95
Gallardo E, Queiroz JA (2008) Biomed Chromatogr 22:795
Langman LJ, Kapur BM (2006) Clin Biochem 39:498
Mullangi R, Agrawal S, Srinivas NR (2009) Biomed Chromatogr 23:3
Palmeri A, Pichini S, Pacifici R et al (2000) Clin Pharmacokinet 38:95
Oxley JC, Smith JL, Kirschenbaum LJ et al (2008) J Forensic Sci 53:690
Efremenko I, Zach R, Zeiri Y (2007) J Phys Chem C 111:11903
Boumba VA, Ziavrou KS, Vougiouklakis T (2006) Int J Toxicol 25:143
Fan VS, Savage RE, Buckley TJ (2007) Toxicol Mech Methods 17:295
Potts RO, Guy RH (1992) Pharm Res 9:663
Reifenrath WG, Kammen HO, Palmer WG et al (2002) Toxicol Appl Pharmacol 182:160
Reddy G, Allen NA, Major MA (2008) Toxicol Mech Methods 18:575
Reifenrath WG, Kammen HO, Reddy G et al (2008) J Toxicol Env Health Part A 71:486
Furge LL, Guengerich FP (2006) Biochem Mol Biol Educ 34:66
Guengerich FP (2006) Aaps Journal 8:E101
Lee MY, Dordick JS (2006) Curr Opin Biotechnol 17:619
Isin EM, Guengerich FP (2008) Anal Bioanal Chem 392:1019
Hodgson E, Rose RL (2007) Pharmacol Ther 113:420
Wang YH, Li Y, Li YH et al (2006) J Phys Chem B 110:10139
Lewis DFV (2003) Pharmacogenomics 4:387
Guengerich FP (2001) Curr Drug Metab 2:93
Guengerich FP (2001) Chem Res Toxicol 14:611
Zamek-Gliszczynski MJ, Hoffmaster KA, Nezasa K et al (2006) Eur J Pharm Sci 27:447
Brandon EFA, Raap CD, Meijerman I et al (2003) Toxicol Appl Pharmacol 189:233
Dalvie D, Obach RS, Kang P et al (2009) Chem Res Toxicol 22:357
Plant N (2004) Drug Discov Today 9:328
Leung KH, Yao M, Stearns R et al (1995) Chem-Biol Interact 97:37
Sabbioni G, Liu YY, Yan HF et al (2005) Carcinogenesis 26:1272
Bhushan B, Halasz A, Thiboutot S et al (2004) Biochem Biophys Res Commun 316:816
Gorontzy T, Drzyzga O, Kahl MW et al (1994) Crit Rev Microbiol 20:265
Spain JC (1995) Annu Rev Microbiol 49:523
Yinon J (1990) Toxicity and metabolism of explosives. CRC, Boca Raton
Y. Kucukardali, H. V. Acar, S. Ozkan et al (2003) Accidental oral poisoning caused by RDX (cyclonite): a report of 5 cases GATA Haydarpasa Training Hospital, 81327 Uskudar, Istanbul, Turkey., pages 42-6
von Moltke LL, Greenblatt DJ, Granda BW et al (1999) Br J Clin Pharmacol 48:89
Hazardous Substances Database (HSDB) (2009) National Library of Medicine—Toxnet: Bethesda. http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?HSDB. Accessed: 18 Feb. 2009
Tanaka E, Nakamura T, Terada T et al (2005) Basic Clin Pharmacol Toxicol 96:88
Wen B, Coe KJ, Rademacher P et al (2008) Chem Res Toxicol 21:2393
Beller HR, Tiemeier K (2002) Environ Sci Technol 36:2060
Chen HW, Li M, Jin QH et al (2006) Chin J Anal Chem 34:839
Florian J, Gao L, Zhukhovskyy V et al (2007) J Am Soc Mass Spectrom 18:835
Gapeev A, Sigman M, Yinon J (2003) Rapid Commun Mass Spectrom 17:943
Major MA, Reddy G, Berge MA et al (2007) J Toxicol Environ Health A 70:1191
Mathis JA, McCord BR (2005) Rapid Commun Mass Spectrom 19:99
Pan XP, Zhang BH, Tian K et al (2006) Rapid Commun Mass Spectrom 20:2222
Sigman ME, Armstrong PA, MacInnis JM et al (2005) Anal Chem 77:7434
Song LG, Bartmess JE (2009) Rapid Commun Mass Spectrom 23:77
Sabbioni G, Rumler R (2007) Biomarkers 12:559
Sabbioni G, Sepai O, Norppa H et al (2007) Biomarkers 12:21
Schmidt AC, Niehus B, Matysik FM et al (2006) Chromatographia 63:1
Rawden HC, Carlile DJ, Tindall A et al (2005) Xenobiotica 35:603
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This work was partially supported by funding from the National Institute of Justice, award number #2001-RC-CX-K003.
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Bell, S.C., Gayton-Ely, M. & Nida, C.M. Bioassays for bomb-makers: proof of concept. Anal Bioanal Chem 395, 401–409 (2009). https://doi.org/10.1007/s00216-009-2851-4
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DOI: https://doi.org/10.1007/s00216-009-2851-4