Gas chromatographic/tandem mass spectrometric identification and quantitation of metabolic 4-acetyltoluene-2,4-diamine from the F344 rat

✍ Scribed by Michael J. Bartels; Charles Timchalk; Fred. A. Smith

• Book ID: 102772690
• Publisher: John Wiley and Sons
• Year: 1993
• Tongue: English
• Weight: 540 KB
• Volume: 22
• Category: Article
• ISSN: 1076-5174
• DOI: 10.1002/bms.1200220309

✦ Synopsis

2,QToluenediamine (TDA) and 2,Qtoluenediisocyanate (TDI) are metabolized in the Fischer 344 rat to monoacetyl-2,Qtoluenediamine (Ac-TDA) and diacetyl-2,Qtoluenediamine (Ac,-TDA). A gas chromatographic/tandem mass spectrometric (GC/MS/MS) method was developed to characterize the structure of the Ac-TDA metabolite (2-acetyl versus Qacetyl), as a D,diacetyl-TDA derivative. This method was also shown to be useful in the measurement of urinary levels of TDA, Ac-TDA and Ac,-TDA. Urine samples (1.0 g) were adjusted to pH 65-7.0, fortified with the internal standard D,-Ac,-TDA (D,-ring + D,-acetyl x 2) and extracted with ethyl acetate (2 x 2 ml). The extract residues were then derivatized with D,-acetic anhydride and analyzed via electron impact GC/MS/MS. MS/MS analysis of the D,-Ac,-TDA derivative of the two Ac-TDA isomers yielded different daughter ion spectra from the common parent ion (m/z 209). Analysis of urine samples from rats administered TDA (P.o., i.v.) and TDI (P.o., inhalation) indicated that all of the metabolic Ac-TDA from these test materials was the Qacetyl-TDA isomer. Subsequent GC/MS analysis of the heptafluorobutyric acid (HFBA) derivative of this metabolite confirmed the MS/MS results. Selected ion monitoring of the M-acetyl daughter ions from the derivatized TDA, Ac-TDA and Ac,-TDA was shown to be a useful technique for quantitation of urinary levels of these compounds, with a detection limit of 35 ng g-' urine for TDA and 10 ng g-' urine for Ac-TDA and AcZ-TDA.