Floyd E. Stanley

A brief introduction to analytical methods in nuclear forensics

Nuclear forensic (NF) techniques are critical in responding to both environmental releases of nuclear materials and illicit trafficking activities involving both nuclear and counterfeit materials. Despite rising need, however, significant barriers exist to the future success of such research. This subset of analytical chemistry contains unique concerns (e.g. chronometry and impurity signatures), a wide variety of preparatory/instrumental approaches, and is in need of innovative solutions to current problems both in and out of the lab. The present work introduces existing NF research, development challenges and notes potential areas for advancement by highlighting several key analytical approaches. Examples of concerns and techniques discussed in this review include: chronometry, reference materials, separations, counting spectrometry, mass spectrometry and more.

Rapid determination of surfactant critical micelle concentrations using pressure-driven flow with capillary electrophoresis instrumentation

This work demonstrates a novel, convenient utilization of capillary electrophoresis (CE) instrumentation for the determination of critical micelle concentrations (CMCs). Solution viscosity differences across a range of surfactant concentrations were monitored by hydrodynamically forcing an analyte towards the detector. Upon reaching the surfactants CMC value, migration times were observed to change drastically. CMC values for four commonly employed anionic surfactants were determined-sodium dodecyl sulfate: 8.1mM; sodium caprylate: 300 mM; sodium decanoate: 86 mM; sodium laurate: 30 mM; and found to be in excellent agreement with values previously reported in the literature. The technique was then applied to the less well-characterized nonionic surfactants poly(oxyethylene) 8 myristyl ether (CMC approximately 9 M), poly(oxyethylene) 8 decyl ether (CMC approximately 0.95 mM) and poly(oxyethylene) 4 lauryl ether.

Validation of reference materials for uranium radiochronometry in the frame of nuclear forensic investigations

The results of a joint effort by expert nuclear forensic laboratories in the area of age dating of uranium, i.e. the elapsed time since the last chemical purification of the material are presented and discussed. Completely separated uranium materials of known production date were distributed among the laboratories, and the samples were dated according to routine laboratory procedures by the measurement of the (230)Th/(234)U ratio. The measurement results were in good agreement with the known production date showing that the concept for preparing uranium age dating reference material based on complete separation is valid. Detailed knowledge of the laboratory procedures used for uranium age dating allows the identification of possible improvements in the current protocols and the development of improved practice in the future. The availability of age dating reference materials as well as the evolvement of the age dating best-practice protocol will increase the relevance and applicability of age dating as part of the tool-kit available for nuclear forensic investigations.

The use of SAX-HPLC–CD as a heparin screening strategy

Heparin, a heterogeneous polysaccharide, has been widely used as an anticoagulant for decades. Recently, however, international events involving the sudden onset of allergic-type reactions following heparin administration led to numerous fatalities, and demanded the use of multiple laborious, time consuming techniques to identify an economically motivated adulterant. Using these methods cooperatively, the semi-synthetic molecule known as oversulfated chondroitin sulfate (OSCS), was found to be present at significant concentrations. Since the discovery of this adulterant, several analytical methods have been put forth or updated to advance the process of screening pharmaceutical heparins; of these, strong anion exchange high performance liquid chromatography (SAX-HPLC) methods have now become routine. In this preliminary work, we report the use of circular dichroism (CD) detection in conjunction with existing SAX-HPLC methods to quantitate various sulfated polysaccharides. The proposed strategy exploits the selectivity associated with CD detection of heparin and heparin-like polysaccharides, while taking advantage of the methods insensitivity to the use of mobile phase additives and programmed gradients. The limit of detection of heparin by CD was found to be ∼0.22 mg/mL, whereas traditional UV/Vis detection yielded a detection limit of ∼1.09 mg/mL. The success of CD detection varied for other polymers, however no significant modifications were made to the separations method to capitalize on the advantages of CD detection.

Forensic investigation of plutonium metal: a case study of CRM 126

In this study, a certified plutonium metal reference material (CRM 126) with a known production history is examined using analytical methods that are commonly employed in nuclear forensics for provenancing and attribution. The measured plutonium isotopic composition and actinide assay are consistent with values reported on the reference material certificate. Model ages from U/Pu and Am/Pu chronometers agree with the documented production timeline. The results confirm the utility of these analytical methods and highlight the importance of a holistic approach for forensic study of unknown materials.

The use of circular dichroism as a simple heparin-screening strategy

Heparin, a heterogeneous polysaccharide, is used extensively as an anticoagulant. Recently, however, tainted heparin was associated with acute reactions that lead to numerous deaths. Extensive investigations ultimately showed oversulfated chondroitin sulfate, a semi-synthetic polysaccharide, to be present in the contaminated samples. These events highlighted the need for new, convenient heparin-screening methods capable of rapidly determining sample purity. In this work, we report the use of circular dichroism spectroscopy to analyze heparin samples for the presence of heparin-like adulterants (e.g., chondroitin sulfate A, dermatan sulfate, and oversulfated chondroitin sulfate) in a simple and straightforward manner. This strategy exploits the subtle differences in the optical properties of each polymer; these differences result from structural dissimilarities. To the best of our knowledge, the findings presented here are the first report of heparin purity screening using traditional spectropolarimetry techniques.

Critical need for plutonium and uranium isotopic standards with lower uncertainties

Certified reference materials (CRMs) traceable to national and international safeguards database are a critical prerequisite for ensuring that nuclear measurement systems are free of systematic biases. CRMs are used to validate measurement processes associated with nuclear analytical laboratories. Diverse areas related to nuclear safeguards are impacted by the quality of the CRM standards available to analytical laboratories. These include: nuclear forensics, radio-chronometry, national and international safeguards, stockpile stewardship, nuclear weapons infrastructure and nonproliferation, fuel fabrication, waste processing, radiation protection, and environmental monitoring. For the past three decades the nuclear community is confronted with the strange situation that improvements in measurement data quality resulting from the improved accuracy and precision achievable with modern multi-collector mass spectrometers could not be fully exploited due to large uncertainties associated with CRMs available from New Brunswick Laboratory (NBL) that are used for instrument calibration and measurement control. Similar conditions prevail for both plutonium and uranium isotopic standards and for impurity element standards in uranium matrices. Herein, the current status of U and Pu isotopic standards available from NBL is reviewed. Critical areas requiring improvement in the quality of the nuclear standards to enable the U. S. and international safeguards community to utilize the full potential of modern multi-collector mass spectrometer instruments are highlighted.

CHIRAL SEPARATIONS USING HEPARIN AND POLYELECTROLYTE MULTILAYERS IN CAPILLARY ELECTROPHORESIS

Reports on the use of heparin as a chiral additive show widely different separation conditions and inconsistent results. A systematic evaluation of the separation of pheniramine enantiomers using heparin as a chiral selector suggested that heparin was interacting with the capillary surface at acidic pH. Further testing confirmed the interaction between heparin and the capillary surface at acidic pH causing an increase in the electroosmotic flow (EOF). Polyelectrolyte multilayer (PEM) was chosen as a potential means to eliminate the interaction between heparin and the capillary surface. Generation of the PEMs on a bare capillary was monitored by measuring the changes in EOF following the deposition of each polyelectrolyte layer; deposition provided consistent EOF intensities and facilitated control over EOF direction. Results from this study indicated that a stable PEM system could be generated, which prevents the interaction of heparin with the capillary surface. This PEM system showed excellent reproducibility, with only a slight loss of resolution due to the increased interactions between the analyte and the charged capillary wall.

Modeling revealed circular dichroism for quinacrine in the presence of heparin.

A simple model is presented that accounts for revealed circular dichroism signals that are observed as a function of enantiopreferential drug binding to a chiral selector. According to this model, the intensity of such signals depends heavily on the differences in enantiomer-selector association constants as well as the differences in bound vs. unbound molar ellipticity values for the chromophore containing species. The proposed model is supported by circular dichroism and capillary electrophoresis results obtained using quinacrine, a tricyclic, antimalarial drug, and heparin, a highly-sulfated glycosaminoglycan. This strategy also explores the role that revealed circular dichroism may play in the optical activity observed for some drugs in the presence of heparin, as has previously been illustrated for chiral drugs in the presence of DNA.

Heparin-induced circular dichroism of chloroquine.

Circular dichroism (CD) and UV/Visible absorption (UV/Vis) spectroscopy techniques were used to investigate the interaction between heparin and chloroquine, an antimalarial drug that has shown potential as an anti-prion agent. CD spectra of rac-chloroquine upon addition of heparin provide evidence of glycosaminoglycan (GAG) binding, support recent findings suggesting that interactions between heparin and antimalarial drugs are largely due to electrostatic interactions, and represent the first reported GAG-induced CD signal of a bicyclic, aromatic compound. The association constant ( approximately 10(3)M(-1)) between chloroquine and heparin was calculated from a UV titration curve and provided additional insight into the nature of the association between these two compounds.