Method development for the measurement of quinone levels in urine.

A method was developed for the quantification of 1-4 ring quinones in urine samples using liquid-liquid extraction followed by analysis with gas chromatography-mass spectrometry. Detection limits for the ten quinones analyzed are in the range 1-2 nmol dm(-3). The potential use of this approach to monitor urinary quinone levels was then evaluated in urine samples from both Sprague-Dawley rats and human subjects. Rats were exposed to 9,10-phenanthraquinone (PQ) by both injection and ingestion (mixed with solid food and dissolved in drinking water). Urinary levels of PQ were found to increase by up to a factor of ten compared to control samples, and the levels were found to depend on both the dose and duration of exposure. Samples were also collected and analyzed periodically from human subjects over the course of six months. Eight quinones were detected in the samples, with levels varying from below the detection limit up to 3 µmol dm(-3).

Development of a gas chromatography/mass spectrometry method to quantify several urinary monohydroxy metabolites of polycyclic aromatic hydrocarbons in occupationally exposed subjects.

The aim of this study was the development of a method for the determination of 12 urinary monohydroxy metabolites of PAHs, namely 1-hydroxynaphthalene, 2-hydroxynaphthalene, 2-hydroxyfluorene, 9-hydroxyfluorene, 1-hydroxyphenanthrene, 2-hydroxyphenanthrene, 3-hydroxyphenanthrene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene. Analytes were determined in the presence of deuterated analogues as internal standards, by GC/MS operating in the electron impact mode. Sample preparation was performed by enzymatic hydrolysis of glucoronate and sulphate conjugates of hydroxy metabolites of PAHs, liquid-liquid extraction with n-hexane, and derivatization with a silylating reagent. The method is very specific, limits of quantification are in the range 0.1-1.4 microg/l, and range of linearity is from limit of detection to 208 microg/l. Within- and between-run precision, expressed as coefficient of variation, are <20%; accuracy for most analytes is within 20% of the theoretical value. An application of the proposed method to the analysis of 10 urine samples from coke-oven workers shows that 1-hydroxynaphthalene and 2-hydroxyfluorene were the most abundant compounds (median 61.4 and 69.7 microg/l, respectively), while 6-hydroxychrysene, and 3-hydroxybenzo[a]pyrene were always below the quantification limit.

Urinary hydroxylated metabolites of polycyclic aromatic hydrocarbons as biomarkers of exposure in asphalt workers.

BACKGROUND: Fumes and vapours released during laying of hot asphalt mix have been recognised as a major source of exposure for asphalt workers. OBJECTIVES: We investigated the relationships between inhalation exposure to asphalt emissions and urinary biomarkers of polycyclic aromatic hydrocarbons (PAHs) in asphalt workers (AW, n=75) and in ground construction workers (CW, n=37). METHODS: Total polyaromatic compounds (PAC) and 15 priority PAHs in inhaled air were measured by personal sampling. Hydroxylated PAH metabolites (OH-PAHs) (2-naphthol, 2-hydroxyfluorene, 3-hydroxyphenanthrene, 1-hydroxypyrene, 6-hydroxychrysene and 3-hydroxybenzo[a]pyrene) were determined in urine spot samples collected in three different times during the work week. RESULTS: Median vapour-phase PAC (5.5 microg m(-3)), PAHs (

Disposition, metabolism, and excretion of the anticancer agent crisnatol in the rat.

Disposition and metabolism of crisnatol (14C-labeled), a novel antitumor agent, was examined after po and iv administration to rats. After both routes of drug administration, there was rapid elimination of the administered radioactivity in the urine (6-12% of the dose) and feces (81-92% of the dose). The drug appeared to be rapidly absorbed after oral dose and there was substantial "first-pass" metabolism. Analysis of the excreta indicated extensive metabolism of crisnatol by the rat, with the intact compound being the major radiolabeled component in the feces (17-20% of dose). Intact drug was not present in urine. Biotransformation of crisnatol by the rat mainly involves oxidation and conjugation pathways. Hydroxylation and dihydrodiol formation in the chrysene ring and oxidation of the propanediol side chain resulted in the formation of the three major fecal metabolites. The principal metabolite in the urine was also a dihydrodiol. Concentrations of intact drug in each tissue assayed exceeded those in plasma, and in the lungs the tissue/plasma ratio approached 300 and 82 at 2 hr after iv and po doses, respectively.

Urinary and faecal excretion of chrysene and chrysene metabolites by rats after oral, intraperitoneal, intratracheal or intrapulmonary application.

The urinary and faecal excretion of chrysene and its phenolic metabolites after oral, intraperitoneal, intratracheal, and intrapulmonary administration to rats have been studied by means of gas chromatography/mass spectrometry. The metabolite profile was found to depend on the mode of excretion and on the route of administration. In all cases the oxidation of chrysene in the 1,2- or 3,4-position predominates, whereas oxidation in the 5,6-position (K-region) seems be a minor pathway.