Analysis of the lidocaine metabolite 2,6-dimethylaniline in bovine and human milk.
2,6-Dimethylaniline (2,6-xylidine; 2,6-DMA) is a nasal carcinogen in rats. Humans may be exposed to this compound via several routes: 2,6-DMA is found in cigarette smoke; it is a pharmacologically inactive metabolite of some drugs (e.g., the local anesthetic lidocaine) and pesticides (e.g., metalaxyl); and it is an impurity in technical grade metalaxyl. The potential transfer of 2,6-DMA from mother to nursing infant via milk is of toxicological concern. Solid-phase microextraction with separation and detection using gas chromatography-mass spectrometry was optimized and used for the analysis of 2,6-DMA in milk. 2,6-DMA-d9 was synthesized and used for quantitation by the isotope ratio method. At a concentration of 5 ppb 2,6-DMA, the method detection limit was 0.20 ppb, and the relative standard deviation was 3.6%. Samples of milk were obtained from bovines administered lidocaine (2.9-3.9 mg/kg) during surgery. A breast milk sample was also obtained from a human donor who received 36 mg lidocaine during dental work. 2,6-DMA was present at levels ranging from 14.5 to 66.0 ppb in bovine milk and was detected at 1.6 ppb in the human milk sample. Our results demonstrate that 2,6-DMA, formed by the metabolism of lidocaine, is transferable to bovine and human milk.
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Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.
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D000328:Adult; D000779:Anesthetics, Local / Q000378:metabolism / Q000493:pharmacokinetics; D000814:Aniline Compounds / Q000032:analysis* / Q000493:pharmacokinetics; D000818:Animals; D001942:Breast Feeding; D002273:Carcinogens / Q000032:analysis* / Q000493:pharmacokinetics; D002417:Cattle; D004781:Environmental Exposure; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008012:Lidocaine / Q000378:metabolism / Q000493:pharmacokinetics; D008892:Milk / Q000737:chemistry*; D008895:Milk, Human / Q000737:chemistry*
D000779:Anesthetics, Local; D000814:Aniline Compounds; D002273:Carcinogens; C007766:2,6-xylidine; D008012:Lidocaine