Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma.
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AbstractPolycyclic aromatic hydrocarbons (PAH) and tobacco-specific nitrosamines, such as 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), are widely accepted to be two important types of lung carcinogens in cigarette smoke. In this study, we have developed a method to estimate individual uptake of these compounds by quantifying r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in 1 mL of smokers' plasma. PheT and NNAL are biomarkers of PAH and NNK uptake, respectively. [D10]PheT and [pyridine-D4]NNAL were added to plasma as internal standards. The plasma was treated with beta-glucuronidase to release any conjugated PheT and NNAL. The analytes were enriched by solid-phase extraction on a mixed mode cation exchange cartridge and the PheT fraction was further purified by high-performance liquid chromatography. The appropriate fractions were analyzed by gas chromatography-negative ion chemical ionization-mass spectrometry for PheT and liquid chromatography-electrospray ionization-mass spectrometry for NNAL. The method was sensitive (limits of quantitation: PheT, 13 fmol/mL; NNAL, 3 fmol/mL), accurate, and precise. Levels of PheT and NNAL in plasma from 16 smokers averaged 95 +/- 71 and 36 +/- 21 fmol/mL, respectively, which are approximately 1% to 2% of the amounts found in urine. This method should be useful in molecular epidemiology studies of carcinogen uptake and lung cancer in smokers.
CitationCancer Epidemiol. Biomarkers Prev. 2006, 15 (8):1490-1494
JournalCancer Epidemiology, Biomarkers & Prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
DescriptionBiomarkers of exposure & effect: method development & validationBiomarker: r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) Exposure/effect represented:exposure to PAH and NNK Tissue: plasma Analytical technicque: GC-MS & HPLC-EI-MS/MS <BR>Sensitivity (LOD): PheT: 13 fmol/ml; NNAL: 3 fmol/ml Accuracy: Spiking plasma which contained 47 fmol/mL PheT, with 50, 100, 150, and 200 fmol/mL PheT, followed by analysis, led to a linear dose-response with r = 0.97 and y intercept = 54 fmol/mL. PheT recovery was 26+11%. Spiking plasma which contained 30 fmol/ml NNAL with 25, 50, 75, and 100 fmol/mL NNAL, followed by analysis, led to a linear dose-response with r = 0.99 and y intercept = 24 fmol/mL. NNAL recovery was 43+21%. Intraday precision: PheT: SD 6.5%; NNAL: SD 7.7% Interday precision: PheT: SD 13.7%; NNAL: SD 11.7%
SponsorsGrant support: National Cancer Institute grants CA-92025 and CA-77598 and NIH grant DA-13333. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.