Simultaneous Quantification of Multiple Urinary Naphthalene Metabolites by Liquid Chromatography Tandem Mass Spectrometry
Ayala, DC; Morin, D; Buckpitt, AR
HERO ID
2902564
Reference Type
Journal Article
Year
2015
Language
English
PMID
| HERO ID | 2902564 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Simultaneous Quantification of Multiple Urinary Naphthalene Metabolites by Liquid Chromatography Tandem Mass Spectrometry |
| Authors | Ayala, DC; Morin, D; Buckpitt, AR |
| Journal | PLoS ONE |
| Volume | 10 |
| Issue | 4 |
| Page Numbers | e0121937 |
| Abstract | Naphthalene is an environmental toxicant to which humans are exposed. Naphthalene causes dose-dependent cytotoxicity to murine airway epithelial cells but a link between exposure and human pulmonary disease has not been established. Naphthalene toxicity in rodents depends on P450 metabolism. Subsequent biotransformation results in urinary elimination of several conjugated metabolites. Glucuronide and sulfate conjugates of naphthols have been used as markers of naphthalene exposure but, as the current studies demonstrate, these assays provide a limited view of the range of metabolites generated from the parent hydrocarbon. Here, we present a liquid chromatography tandem mass spectrometry method for measurement of the glucuronide and sulfate conjugates of 1-naphthol as well as the mercapturic acids and N-acetyl glutathione conjugates from naphthalene epoxide. Standard curves were linear over 2 log orders. On column detection limits varied from 0.91 to 3.4 ng; limits of quantitation from 1.8 to 6.4 ng. The accuracy of measurement of spiked urine standards was -13.1 to + 5.2% of target and intra-day and inter-day variability averaged 7.2 (+/- 4.5) and 6.8 (+/- 5.0) %, respectively. Application of the method to urine collected from mice exposed to naphthalene at 15 ppm (4 hrs) showed that glutathione-derived metabolites accounted for 60-70% of the total measured metabolites and sulfate and glucuronide conjugates were eliminated in equal amounts. The method is robust and directly measures several major naphthalene metabolites including those derived from glutathione conjugation of naphthalene epoxide. The assays do not require enzymatic deconjugation, extraction or derivatization thus simplifying sample work up. |
| Doi | 10.1371/journal.pone.0121937 |
| Pmid | 25853821 |
| Wosid | WOS:000352478400055 |
| Url | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929452741&doi=10.1371%2fjournal.pone.0121937&partnerID=40&md5=a7c2e5576d93b27440b3f179fe76b495 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Sciences: Comprehensive Works; Metabolites; Naphthalenes; Glutathione; Sulfates; Epoxides; Metabolic labeling; Enzyme metabolism; Cytotoxicity; Mass spectrometry; Naphthalene; Liquid chromatography; Biotransformation; Cytochrome; Scientific imaging; Metabolism; Chromatography; Toxicology; Toxicity; Polycyclic aromatic hydrocarbons; Exposure; Lung diseases; Veterinary colleges; Spectroscopy; Veterinary medicine; Mass spectroscopy; Chemicals; Dosimetry; Epithelial cells; Naphthol; Enzymes; Conjugates; Rodents; Respiratory tract; Chronic obstructive pulmonary disease; Quantitation; Analytical methods; Detection limits; Conjugation; Biomarkers; United States--US; Muridae; Macaca mulatta; California |