Isotope Dilution UPLC-APCI-MS/MS Method for the Quantitative Measurement of Aromatic Diamines in Human Urine: Biomarkers of Diisocyanate Exposure.
Urinary diamines are biomarkers of diisocyanate exposure. Diisocyanates are considered as skin and respiratory sensitizers and are the most frequently reported cause of occupational asthma. Herein we report on the development and validation of an ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the measurement of five aromatic diamines, 4,4'-methylenedianiline (MDA), 2,4-toluenediamine (4TDA), 2,6-toluenediamine (6TDA), 1,5-naphthalenediamine (NDA), and p-phenylenediamine (PPDA) in human urine. The method incorporates sample preparation steps, which include a 4 h acid hydrolysis followed by high-throughput solid-phase extraction prior to chromatographic separation. Chromatographic separation was achieved using a C18 reversed phase column with gradient elution of basic mobile phases (pH 9.2). The duty cycle of the method was less than 5 min, including both the column equilibration and autosampler movement. Analytical detection was performed using positive ion atmospheric pressure chemical ionization tandem mass spectrometry (APCI-MS/MS) in scheduled multiple reaction monitoring (sMRM) mode. Excellent linearity was observed over standard calibration curve concentration ranges of 3 orders of magnitude with method detection limit ranging from 10 to 100 pg/mL. The interday and intraday reproducibility and accuracy were within ±15%. This method is fast, accurate, and reproducible and is suitable for assessment of exposure to the most common aromatic diisocyanates within targeted groups as well as larger population studies such as the National Health and Nutrition Examination Survey (NHANES).
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
Deepak
D
Bhandari
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
John
J
Ruhl
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
Anthony
A
Murphy
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
Ernest
E
McGahee
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
David
D
Chambers
Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, Georgia 30341, United States.
Benjamin C
BC
Blount
D000814:Aniline Compounds / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002247:Carbon Isotopes; D002853:Chromatography, Liquid / Q000379:methods; D003959:Diamines / Q000652:urine*; D006801:Humans; D017953:Isocyanates / Q000378:metabolism / Q000633:toxicity; D057230:Limit of Detection; D009281:Naphthalenes / Q000652:urine*; D009587:Nitrogen Isotopes; D053719:Tandem Mass Spectrometry / Q000379:methods
D000814:Aniline Compounds; D015415:Biomarkers; D002247:Carbon Isotopes; D003959:Diamines; D017953:Isocyanates; D009281:Naphthalenes; D009587:Nitrogen Isotopes
Analyst. 1997 Jan;122(1):51-6
9069099
Toxicol Lett. 2002 Aug 5;134(1-3):259-64
12191886
Carcinogenesis. 1995 Oct;16(10):2583-7
7586170
Toxicol Rep. 2014;1:743-751
26877973
Biomarkers. 2003 May-Aug;8(3-4):204-17
12944173
Eur Respir J. 2002 Feb;19(2):377-80
11866019
Occup Med (Lond). 2007 Sep;57(6):391-3
17728308
J Occup Environ Hyg. 2004 Dec;1(12):789-98
15742708
J Allergy Clin Immunol. 2009 Mar;123(3):519-28; quiz 529-30
19281900
IARC Monogr Eval Carcinog Risks Hum. 1999;71 Pt 1:1-315
10507919
Arch Toxicol. 2004 Jul;78(7):378-83
15007542
Ann Occup Hyg. 2004 Jul;48(5):415-24
15240338
Anal Bioanal Chem. 2013 Sep;405(23):7205-13
23839327
Int Arch Occup Environ Health. 2005 Aug;78(7):541-6
15995877
J Chromatogr. 1986 Oct 3;367(2):385-92
3023414
J Occup Environ Med. 2015 Jan;57(1):44-51
25563538
Analyst. 2004 Jun;129(6):522-8
15152330
Toxicol Appl Pharmacol. 1994 Feb;124(2):181-90
8122263
N Engl J Med. 1974 Aug 8;291(6):278-82
4407276
Ann Occup Hyg. 2011 Mar;55(2):127-31
21252056
Chem Res Toxicol. 2000 Feb;13(2):82-9
10688531
Analyst. 1986 Sep;111(9):1069-71
3022617
Analyst. 1985 Aug;110(8):893-905
2998224
J Occup Med Toxicol. 2011 Mar 29;6(1):9
21447151