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Rapid Commun Mass Spectrom. 2002;16(24):2239-48.

Liquid chromatography/electrospray tandem mass spectrometry characterization of styrene metabolism in man and in rat.

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Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, Laboratorio di Tossicologia Industriale, Università degli Studi di Parma, Via Gramsci 14, 43100 Parma, Italy.


Liquid chromatography with electrospray tandem mass spectrometry was used to characterize the metabolism of styrene in man and in rat. To improve identification and characterization of minor styrene metabolites, rats were co-exposed to styrene and styrene-d(8). In addition to the main styrene metabolites, mandelic acid and phenylglyoxylic acid, and specific mercapturic acids, phenylhydroxyethylmercapturic acids (PHEMAs), other minor metabolites, including phenylglycine, N-acetyl-S-(phenacyl)cysteine, 4-vinylphenol and styreneglycol conjugates (glucuronides and sulfates) were identified and determined both in human and rat urine. Phenylglycine and N-acetyl-S-(phenacyl)cysteine have been hypothesized to occur, but never detected in human or rat urine after styrene exposure. 4-Vinylphenol and styrene glycol had already been recognized as styrene metabolites, but never determined as intact glucuronide and sulfate conjugates. Failure to identify 1- and 2-phenylethanol conjugates suggests that phenylethanol might be an intermediate metabolite, but it is not a conjugated catabolite. A method for the simultaneous determination of mandelic acid, phenylglyoxylic acid, phenyglycine and the four PHEMA diastereoisomers has been developed and validated. For those glucuronide and sulfate conjugates whose standards are not commercially available, a method for semiquantitative analysis, based on the use of structurally similar compounds as standards, has been developed. This approach was found to be valid for the determination of 4-vinylphenol glucuronide and 4-vinylphenol sulfate.

[Indexed for MEDLINE]

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