doi:

DOI: 10.3724/SP.J.1096.2013.30245

Chinese Journal of Analytical Chemistry (分析化学) 2013/41:12 PP.1801-1806

A New High Performance Liquid Chromatography Tandem Mass Spectrometric Method for Quantitative Determination of Soman-tyrosine Adduct in Exposed Rat Plasma


Abstract:
Towards the urgent need of accurately retrospective analysis of biomedical samples exposed by nerve agent soman (GD), we developed a new quantitative method of GD-tyrosine adduct (GD-Tyr) in exposed rat plasma by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) with high sensitivity and high specificity. After a series of pretreatment procedures including extraction of albumin by affinity chromatography and ultrafiltration, enzymatic hydrolysis by pronase, and solid phase extraction, we qualitatively and quantitatively determined soman-tyrosine adduct by reversed-phase LC-triple quadrupole MS in the positive electrospray ionization and multiple reactions monitoring mode. The monitored transitions were m/z 260/214 (GD-Tyr) and m/z 293/247(internal standard). A good linearity was obtained in the range of 0.1-500 μg/L for GD-Tyr (R2=0.999) with a limit of detection of 0.02 μg/L and a limit of quantification of 0.05 μg/L. The recovery of GD-Tyr was in the range of 90.1%-103.5%, and the RSD of this method was less than 3%. We then investigated the toxicokinetics of GD-Tyr for GD exposed SD rat (n=5) in an intraperitoneal injection way. An obvious time and dose dependent relationship between GD-Tyr and the dose of soman was observed. We suggest that GD-tyrosine adduct can be used as an exposure biomarker to the retrospective detection of soman after exposure.

Key words:Soman,Soman-tyrosine adduct,Liquid chromatography-tandem mass spectrometry,Plasma,Toxicokinetics

ReleaseDate:2015-04-19 11:07:49



白海红, 郭 磊, 冯建林, 冯翠玲, 陈 佳, 谢剑炜. 分析化学, 2008, 36(9): 1269-1272

1 Renner J A, Dabisch P A, Evans R A, McGuire J M, Totura A L, Jakubowski E M, Thomson S A. Journal of Analytical Toxicology, 2008, 32: 92-98

2 Carol-Visser J, Schans M, Fidder A, Hulst A G, Baar B L M, Irth H, Noort D. J. Chromatogr. B, 2008, 870: 91-97

3 Kataoka M, Seto Y. J. Chromatogr. B, 2003, 795: 123-132

4 BAI Hai-Hong, GUO Lei, FENG Jian-Lin, FENG Cui-Ling, CHEN Jia, XIE Jian-Wei. Chinese J. Anal. Chem., 2008, 36(9): 1269-1272

5 Knaack J S, Zhou Y, Abney C W, Jacob J T, Prezioso S M, Hardy K, Lemire S W, Thomas J, Johnson R C. Anal. Chem., 2012, 84(21): 9470-9477

6 Koller M, Becker C, Thiermann H, Worek F. J. Chromatogr. B, 2010, 878(17-18): 1226-1233

7 Gab J, John H, Blum M M. Toxicol. Lett., 2011, 200(1-2): 34-40.

8 Black R M. Journal of Analytical Toxicology, 2008, 32: 2-9

9 Li B, Nachon F, Froment M T, Verdier L, Debouzy J C, Brasme B, Gillon E, Schopfer L M, Lockridge O, Masson P. Chem. Res. Toxicol., 2008, 21(2): 421-431

10 Williams N. H, Harrison J. M, Read R. W, Black R. M. Arch. Toxicol., 2007, 81: 627-639

11 Read R W, Riches J R, Stevens J A, Stubbs S J, Black R M. Arch. Toxicol., 2010, 84: 25-26

12 Li B, Schopfer L M, Hinrichs S H, Masson P, Lockridge O. Anal. Biochem., 2007, 361: 263-272

13 Peeples E S, Schopfer L M, Duysen E G, Spaulding R, Voelker T, Thompson C M, Lockridge O. Toxicological Sciences, 2005, 83: 303-312

14 Black R.M, Harrison J.M, Read R.W. Arch. Toxicol., 1999, 73: 123-126

15 Ding S J, Carr J, Carlson J E, Tong L, Xue W, Li Y, Schopfer L M, Li B, Nachon F, Asojo O, Thompson C M, Hinrichs S H, Masson P, Lockridge O. Chem. Res. Toxicol., 2008, 21: 1787-1794

16 Chen S, Zhang J, Lumley L, Cashman J R. J. Pharmacol. Exp. Ther., 2013, 344(2): 531-541

17 Li B, Ricordel I, Schopfer LM, Baud F, Megarbane B, Nachon F, Masson P, Lockridge O. Toxicological Sciences, 2010, 116(1): 23-31

18 Bao Y, Liu Q, Chen J, Lin Y, Wu B D, Xie J W. J. Chromatogr. A, 2012, 1229: 164-171

19 U. S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), Center for Veterinary Medicine (CVM), Guidance for Industry, Bioanalytical Method Validation, 2001