Stereochemical aspects of styrene biotransformation

Linhart, Igor; Šmejkal, J.; Mládková, Ivana

doi:10.1016/s0378-4274(97)00111-2

Cited by 19 publications

(24 citation statements)

References 27 publications

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“…Similar values have been found in other studies, in humans [16] as well as in rats [21] and mice [22]. It has been suggested in those studies that this higher excretion of (S)-MA could be due to productenantioselectivity of the oxidation of styrene to SO.…”

Section: Discussionsupporting

confidence: 90%

“…Little is known about the stereochemistry of these metabolic steps, certainly in humans. SG is assumed to be enantiospeci®cally metabolised to MA [17], but this assumption can be questioned on the basis of studies in rats [21] and mice [22]. Renal clearance of the MA enantiomers has not been investigated so far, but several organic acids are known to be excreted by tubular secretion [25], and on the basis of our CL r data for conjugated SG, di erences in tubular excretion between the MA enantiomers might be expected.…”

Section: Discussionmentioning

confidence: 99%

“…A number of studies have addressed the stereometabolism of styrene, but most of them have been performed in vitro [3,5,6,31] or in vivo in laboratory animals, e.g. rats and mice [7,8,21,22,32]. The few studies performed in humans only measured enantiomers of MA [10,13,18].…”

Section: Introductionmentioning

confidence: 99%

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Stereochemical metabolism of styrene in volunteers

Wenker

Kežić

Monster

et al. 2001

Int Arch Occup Environ Health

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Stereochemical metabolism of styrene in volunteersWenker, M.A.M.; Kezic, S.; Monster, A.C.; de Wolff, F.A. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Objectives: To study the stereochemistry of styrene metabolism in volunteers, and its interindividual variability. Methods: Twenty healthy male volunteers (aged 18±37 years) were exposed to 360 mg/m 3 styrene for 1 h while they performed 50 W physical exercise. Venous blood was drawn during and for up to 2 h after exposure. Urine was collected at time-intervals up to 24 h after exposure. The following parameters were determined: styrene, free and conjugated styrene glycol (SG) in blood, and conjugated SG, mandelic acid (MA) and phenylglyoxylic acid (PGA) in urine. Results: Average pulmonary retention of styrene was 62%. Excretion of the acidic metabolites MA and PGA accounted for 58% of the pulmonary uptake. The average maximum concentration (C max ) and area under the curve (AUC) of free (R)-SG in blood were 1.3 and 1.7 times higher than those of (S)-SG respectively; the half-life of (R)-SG was longer (82 vs 62 min, P < 0.005). C max and AUC of the conjugated SG enantiomers in blood did not di er, but again half-life for (R)-SG was longer (72 vs 64 min, P < 0.05). Cumulative excretion and renal clearance of conjugated (S)-SG in urine were three and four times higher, respectively, than that of (R)-SG. Cumulative excretion of (S)-MA was 1.6 times higher than (R)-MA. Interindividual di erences in the kinetic parameters of the metabolites were two-to threefold. Conclusions: The enantiomeric excess found was di erent for each metabolite under study, implying di erent enantioselectivity and/or enantiospeci®city of the enzymes and carrier-proteins involved in the biotransformation and excretion. The use of these metabolites as biological indicators for prediction of the enantiomeric excess of the toxic metabolite styrene-7,8-oxide (SO) is therefore not justi®ed. Interindividual di erences in the stereochemical metabolism of styrene are moderate.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

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Stereochemical metabolism of styrene in volunteers

Wenker

Kežić

Monster

et al. 2001

Int Arch Occup Environ Health

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“…3 Both styrene epoxide and 1,2-phenylethanediol are chirals and show stereo-selectivity in metabolism in vivo leading to different urinary excretions of MA enantiomers. 4 MA and its derivatives are a type of chiral synthons which are useful for the production of different pharmaceuticals, such as cephalosporins, antiobesity agents, semisynthetic penicillins and antitumor agents. 5,6 The few reported methods for the determination of MA are HPLC, 7 gas-chromatography, 8,9 capillary electrophoresis, 10 electrochemiluminescence 11 and spectrophotometry.…”

Section: Introductionmentioning

confidence: 99%

A Sensitive Procedure for the Rapid Determination of Mandelic Acid by Flow Injection Analysis and Chemiluminescence Detection

Alam¹,

Jeon²,

Karim³

et al. 2009

Bulletin of the Korean Chemical Society

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A rapid and sensitive chemiluminescence (CL) method using flow-injection (FI) has been developed for the determination of mandelic acid which is based on the enhancement of mandelic acid to the CL intensity of Ru(bipy)3 2+ -Ce(IV) system. The enhancement effect was dependent on the concentration of mandelic acid, based on which, CL system was established for the determination of mandelic acid. The concentrations of Ru(bipy)3 2+ , Ce(IV), and H2SO4 were optimized. Under the optimum experimental conditions, the linear range and detection limit are 1.46-342.0 μg/mL and 0.072 μg/mL, respectively. The correlation coefficient (R) was 0.99732. The utility of this method was demonstrated by determining mandelic acid in capsules and human urine sample.

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“…1). Stereochemical aspects of styrene biotransformation in rat have been recently investigated by Linhart et al 5 Via a S N 2 mechanism, R-SO yields stereospecifically S,R-M1 and R,R-M2, whereas S-SO gives only R,R-M1 and S,R-M2.…”

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confidence: 99%

A new method for the analysis of styrene mercapturic acids by liquid chromatography/electrospray tandem mass spectrometry

Manini

Andreoli

Bergamaschi

et al. 2000

Rapid Commun. Mass Spectrom.

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A new method based on liquid chromatography/tandem mass spectrometry has been developed for the direct determination of specific urinary mercapturic acids arising from the conjugation of (R)‐and (S)‐enantiomers of styrene 7,8‐oxide with glutathione (GSH), i.e. (R,R)‐ and (S,R)‐N‐acetyl‐S‐(1‐phenyl‐2‐hydroxyethyl)cysteine (R,R‐M1 and S,R‐M1) and (R,R)‐ and (S,R)‐N‐acetyl‐S‐(2‐phenyl‐2‐hydroxyethyl)cysteine (R,R‐M2 and S,R‐M2). The four diastereoisomers were separated on a C18‐DB (7.5 cm, 3 µm) column using variable proportions of 20 mM aqueous ammonium formate buffer and methanol at a flow‐rate of 0.5 mL/min. The analytes were ionized by electrospray, in negative‐ion mode. Operating in selected‐reaction monitoring mode, linearity of the MS response versus analyte concentration was established over 4 orders of magnitude, the detection limits being 0.7–1.0 µg/L for all the mercapturates. Precision of the method determined at 50 µg/L (n = 12), expressed as relative standard deviation, was respectively 3.1, 4.8 and 6.9% within the run, intra‐day and inter‐day. The corresponding figures at 1.0 mg/L (n = 12) were respectively 2.0, 3.6 and 5.5%. The method was applied to the quantitative analysis of conjugated metabolites in urine samples from workers occupationally exposed to styrene. The diastereoisomers R,R‐M1 and S,R‐M2 accounted respectively for 50 and 40% of total mercapturates, whereas the proportion of R,R‐M2 was 7% and only minor amounts of S,R‐M1 were detectable. Styrene mercapturates represented a minor fraction of total styrene metabolites, less than 1% on average. The ratio mercapturates/main metabolites (mandelic + phenylglyoxylic acid) showed a bimodal distribution, the medians of the two subgroups being 0.2 and 1%, respectively. Such subgroups are probably characterized by the genetic polymorphisms of the drug‐metabolizing enzymes to be identified. Copyright © 2000 John Wiley & Sons, Ltd.

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Stereochemical aspects of styrene biotransformation

Cited by 19 publications

References 27 publications

Stereochemical metabolism of styrene in volunteers

Stereochemical metabolism of styrene in volunteers

A Sensitive Procedure for the Rapid Determination of Mandelic Acid by Flow Injection Analysis and Chemiluminescence Detection

A new method for the analysis of styrene mercapturic acids by liquid chromatography/electrospray tandem mass spectrometry

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