Abstract
(E)-1,1,4,4-tetramethyl-2-tetrazene (TMTZ) is formed from the oxidation of the unsymmetrical 1,1-dimethylhydrazine (UDMH) and is used as a storable liquid fuel which can be considered as a new potential propellant for space rocket propulsion. To better understand the toxicological behavior of the compound, an intraperitoneal administration of TMTZ was performed in mice to define its toxicokinetics and tissue distribution. A fully validated liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) assay was developed to determine TMTZ levels in biological samples. Determination of TMTZ was achieved using 50 μL of plasma or tissue solution. Precipitation with ammonium sulfate and acetonitrile was used for sample preparation. Liquid chromatography was performed on an Atlantis HILIC Silica column (Waters; 3 μm, 150 mm × 2.1 mm i.d.). Isocratic elution with a mixture of ammonium acetate buffer (pH 5, 100 mM)/water/acetonitrile (3:2:95, v/v/v) was used. The detection was conducted using an electrospray source in positive ion mode. TMTZ and 15N2-TMTZ (internal standard) were quantitated in selected reaction monitoring mode using the transition m/z 117→72 and 119→74, respectively. Standard curves exhibited excellent linearity in the range of 10–500 ng/mL for plasma and 50–2000 ng/mL for all tissues (heart, liver, brain, kidney, and lung) analyzed, and acceptable precision and accuracy (<10 %) were obtained. The elimination rate constant strongly suggests that TMTZ was very quickly eliminated from the body. The results of tissue distribution experiments indicated that TMTZ underwent a rapid distribution into limited organs such as the liver, kidney, and brain.
Similar content being viewed by others
References
Choudhary G, Hansen H (1998) Human health perspective on environmental exposure to hydrazines: a review. Chemosphere 37:801–843
Carlsen L, Kenessov BN, Batyrbekova SY, Kolumbaeva SZ, Shalakhmetova TM (2009) Assessment of the mutagenic effect of 1,1-dimethyl hydrazine. Environ Toxicol Pharmacol 28:448–452
Reddy G, Song J, Mecchi MS, Johnson MS (2010) Genotoxicity assessment of two hypergolic energetic propellant compounds. Mutat Res 700:26–31
Carlsen L, Kenesova OA, Batyrbekova SE (2007) A preliminary assessment of the potential environmental and human health impact of unsymmetrical dimethylhydrazine as a result of space activities. Chemosphere 67:1108–1116
Miro Sabate C, Delalu H, Guelou Y, Dhenain A, Perrut C, (2011) Préparation d’alkyltetrazenes. Patent FR1153221
Carlsen L, Kenessov BN, Batyrbekova SY (2009) A QSAR/QSTR study on the human health impact of the rocket fuel 1,1-dimethyl hydrazine and its transformation products multicriteria hazard ranking based on partial order methodologies. Environ Toxicol Pharmacol 27:415–423
Kenessov B, Alimzhanova M, Sailaukhanuly Y, Baimatova N, Abilev M, Batyrbekova S, Carlsen L, Tulegenov A, Nauryzbayev M (2012) Transformation products of 1,1-dimethylhydrazine and their distribution in soils of fall places of rocket carriers in Central Kazakhstan. Sci Total Environ 427–428:78–85
Ponomarenko SA, Smolenkov AD, Shpigun OA (2009) Determination of 1,1-dimethylhydrazine and its decomposition products using ion-pair chromatography. Mosc Univ Chem Bull 64:147–153
Smolenkov AD, Ponomarenko SA, Shpigun OA, (2009) The retention of 1,1-dimethylhydrazine and its decomposition products on alkyl-grafted silica gels under the ion pair chromatography conditions. Russ J Phys Chem 83:478–487
Kenessov B, Sailaukhanuly Y, Koziel JA, Carlsen L, Nauryzbayev M (2011) GC-MS and GC-NPD determination of formaldehyde dimethylhydrazone in water using SPME. Chromatographia 73:123–128
Kenessov BN, Koziel JA, Grotenhuis T, Carlsen L (2010) Screening of transformation products in soils contaminated with unsymmetrical dimethylhydrazine using headspace SPME and GC-MS. Anal Chim Acta 674:32–39
TOXNET, http://toxnet.nlm.nih.gov/cgi-bin/sis/search/a?dbs+hsdb:@term+@DOCNO+1172. TOXNET data network
Bingham E, Cohrssen B, Powell CH, (2001) Patty’s toxicology, volumes 1-9. V4 1293
Hawks A, Hicks RM, Holsman JW, Magee PN (1974) Morphological and biochemical effects of 1,2-dimethylhydrazine and 1-methylhydrazine in rats and mice. Br J Cancer 30:429–439
Acknowledgments
We thank Emilie Henin (EMR 3738, Laboratoire de Ciblage Thérapeutique en Cancérologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France) for her assistance in the determination of the pharmacokinetic parameters. We also thank Sarah Kabani for her help in reviewing the English of the manuscript.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Payen, L., Honorat, M., Bouard, C. et al. Quantification and kinetic study in plasma and tissues of (E)-1,1,4,4-tetramethyl-2-tetrazene, a liquid propellant and a transformation product of 1,1-dimethyl hydrazine. Anal Bioanal Chem 407, 6721–6729 (2015). https://doi.org/10.1007/s00216-015-8829-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-015-8829-5