Detection of cotinine in newborn dried blood spots
ABSTRACT Maternal smoking while pregnant is a plausible risk factor for childhood cancers because many seem to initiate in utero and tobacco-specific carcinogens cross the placenta. Social desirability bias may affect maternal report of smoking in case-control studies and could explain inconsistently observed associations with offspring cancer. Detection of tobacco smoke biomarkers in dried blood spots (DBS), which are increasingly stored by newborn screening programs, may improve retrospective assessment of fetal tobacco exposure. As proof-of-principle, we examined cotinine in DBS of 20 infants enrolled in a pilot study of pregnancy among low-income women. We recruited 107 pregnant women (<30 weeks of gestation) from six Women, Infants, and Children clinics in Minneapolis and St. Paul in 1999. Blood samples obtained at enrollment were tested for total cotinine using gas chromatography/mass spectrometry. Women were then interviewed at 7 months of gestation to determine current smoking habits. DBS were obtained from the Minnesota Department of Health. We tested DBS from 10 infants whose mothers had detectable serum cotinine at baseline and 10 control infants whose mothers had none. One quarter of each DBS was assayed for cotinine using gas chromatography/mass spectrometry; levels were estimated assuming 50 muL blood per sample. Mean cotinine was 29 ng/mL (SD, 7.5), 45 ng/mL (SD, 9.7), and 9 ng/mL (SD, 7.4), respectively, among infants of all smokers, infants of four women who acknowledged smoking at 7 months of gestation, and infants of nonsmokers. These results suggest that DBS analysis may identify infants of women who smoke throughout pregnancy.
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ABSTRACT: Dried blood spot (DBS) sampling and DBS analysis have increasingly received attention during recent years. Furthermore, a substantial number of DBS methods has recently become available in clinical, forensic and occupational toxicology. In this review, we provide an overview of the different DBS-based methods that have been developed for detecting (markers of) abused substances. These include both legal and illegal drugs belonging to different categories, including cannabinoids, cocaine and metabolites, opioids, benzodiazepines and Z-drugs, amphetamines and analogs, gamma-hydroxybutyric acid, ketamine and novel psychoactive substances such as cathinones. Markers of ethanol consumption and tobacco use are also covered in this review. Since the majority of published methods has shown promising results overall, an interesting role for DBS analysis in diverse toxicological applications can be envisaged. For the distinct applications, we discuss the specific potential and benefits of DBS, the associated limitations and challenges, as well as recent developments and future perspectives.Bioanalysis 08/2014; 6(17):2211-27. DOI:10.4155/bio.14.156 · 3.03 Impact Factor
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ABSTRACT: Dried blood spots (DBSs) can provide accurate and valuable estimates of exposure to environmental toxicants, and the use of information derived from archived newborn DBSs has enormous potential to open up new research on the impacts of early chemical exposure on disease. Broad application of DBS for the purpose of quantitative exposure estimation requires robust and validated methods. This study investigates the suitability of DBS analyses for population studies of exposure to three chemical groups: polychlorinated biphenyls (PCBs), brominated flame retardants (BFRs), and chlorinated pesticides. It examines background (matrix) contamination, recovery and extraction variability, sensitivity, and storage stability. DBS samples prepared using 50μL of adult blood were analyzed by GC/MS, and method performance was confirmed by using certified materials and paired DBS-blood samples from six volunteers. Several of the target compounds and their degradation products have not been previously measured in DBSs. All target compounds were detected in DBS samples collected from the volunteers. Sample DBS cards showed background contamination of several compounds. When stored at room temperature, target compounds, excluding PBDEs, were stable for up to one month. When refrigerated or frozen, stability was acceptable for all compounds up to one year, and multiyear storage appears acceptable at colder (e.g., -80°C) temperatures. Multicompartment models may be used to estimate or correct for storage losses. Considering concentrations of contaminants for adults and children reported in the literature, and experimental values of detection limits and background contamination, DBS samples are suitable for quantifying exposures to many PCBs, BFRs and persistent pesticides.Science of The Total Environment 07/2014; 494-495C:252-260. DOI:10.1016/j.scitotenv.2014.06.142 · 3.16 Impact Factor
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ABSTRACT: Dried blood spots (DBS) typically consist in the deposition of small volumes of capillary blood onto dedicated paper cards. Comparatively to whole blood or plasma samples, their benefits rely in the fact that sample collection is easier and that logistic aspects related to sample storage and shipment can be relatively limited, respectively, without the need of a refrigerator or dry ice. Originally, this approach has been developed in the sixties to support the analysis of phenylalanine for the detection of phenylketonuria in newborns using bacterial inhibition test. In the nineties tandem mass spectrometry was established as the detection technique for phenylalanine and tyrosine. DBS became rapidly recognized for their clinical value: they were widely implemented in pediatric settings with mass spectrometric detection, and were closely associated to the debut of newborn screening (NBS) programs, as a part of public health policies. Since then, sample collection on paper cards has been explored with various analytical techniques in other areas more or less successfully regarding large-scale applications. Moreover, in the last 5 years a regain of interest for DBS was observed and originated from the bioanalytical community to support drug development (e.g., PK studies) or therapeutic drug monitoring mainly. Those recent applications were essentially driven by improved sensitivity of triple quadrupole mass spectrometers. This review presents an overall view of all instrumental and methodological developments for DBS analysis with mass spectrometric detection, with and without separation techniques. A general introduction to DBS will describe their advantages and historical aspects of their emergence. A second section will focus on blood collection, with a strong emphasis on specific parameters that can impact quantitative analysis, including chromatographic effects, hematocrit effects, blood effects, and analyte stability. A third part of the review is dedicated to sample preparation and will consider off-line and on-line extractions; in particular, instrumental designs that have been developed so far for DBS extraction will be detailed. Flow injection analysis and applications will be discussed in section IV. The application of surface analysis mass spectrometry (DESI, paper spray, DART, APTDCI, MALDI, LDTD-APCI, and ICP) to DBS is described in section V, while applications based on separation techniques (e.g., liquid or gas chromatography) are presented in section VI. To conclude this review, the current status of DBS analysis is summarized, and future perspectives are provided. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 9999:1–78, 2014Mass Spectrometry Reviews 09/2014; DOI:10.1002/mas.21441 · 8.05 Impact Factor