Method performance and clinical workflow outcomes associated with meconium and umbilical cord toxicology testing.

OBJECTIVE: Neonatal abstinence syndrome (NAS) is a rising concern with unknown long-term effects. It is apparent that higher cost of care, impact on the community and reduced quality of life are associated with similar etiologies (e.g., fetal alcohol syndrome). Detection of drug exposure in utero allows for earlier intervention to potentially reduce undesired outcomes. Umbilical cord tissue (UCT) has been documented as a readily accessible specimen for detection of drug exposure and has emerged as an alternative specimen to meconium. METHODS: The analytical and clinical impact of umbilical cord tissue relative to meconium was evaluated for assessment of in utero drug exposure. Quality metrics relating to turnaround-time and diagnosis of NAS were investigated after switching from meconium to UCT. RESULTS: Umbilical cord tissue showed higher clinical sensitivity but lower specificity for prediction of NAS diagnosis. Birth to result time decreased with adoption of UCT. CONCLUSIONS: Birth to result time decreased by the switching to UTC as well as the number of missed collections. The clinical sensitivity and negative predictive value for NAS increased with UCT; however both meconium and UTC samples were negative for opiates for a significant percentage of newborns with a diagnosis of NAS.

A (Fluoroalkyl)Guanidine Modulates the Relaxivity of a Phosphonate-Containing T1-Shortening Contrast Agent.

Responsive magnetic resonance imaging (MRI) contrast agents, those that change their relaxivity according to environmental stimuli, have promise as next generation imaging probes in medicine. While several of these are known based on covalent modification of the contrast agents, fewer are known based on controlling non-covalent interactions. We demonstrate here accentuated relaxivity of a T1-shortening contrast agent, Gd-DOTP5- based on non-covalent, hydrogen bonding of Gd-DOTP5- with a novel fluorous amphiphile. By contrast to the phosphonate-containing Gd-DOTP5- system, the relaxivity of the analogous clinically approved contrast agent, Gd-DOTA- is unaffected by the same fluorous amphiphile under similar conditions. Mechanistic studies show that placing the fluorous amphiphile in proximity of the gadolinium center in Gd-DOTP5- caused an increase in τ m (bound-water residence lifetime or the inverse of water exchange rate, τ m = 1/kex) and an increase in τ R (rotational correlation time), with τ R being the factor driving enhanced relaxivity. Further, these effects were not observed when Gd-DOTA- was treated with the same fluorous amphiphile. Thus, Gd-DOTP5- and Gd-DOTA- respond to the fluorous amphiphile differently, presumably because the former binds to the amphiphile with higher affinity. (DOTP = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraphosphonic acid; DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid).

Introductory Chemistry: A Molar Relaxivity Experiment in the High School Classroom.

Dotarem and Magnevist, two clinically available magnetic resonance imaging (MRI) contrast agents, were assessed in a high school science classroom with respect to which is the better contrast agent. Magnevist, the more efficacious contrast agent, has negative side effects because its gadolinium center can escape from its ligand. However, Dotarem, though a less efficacious contrast agent, is a safer drug choice. After the experiment, students are confronted with the FDA warning on Magnevist, which enabled a discussion of drug efficacy versus safety. We describe a laboratory experiment in which NMR spin lattice relaxation rate measurements are used to quantify the relaxivities of the active ingredients of Dotarem and Magnevist. The spin lattice relaxation rate gives the average amount of time it takes the excited nucleus to relax back to the original state. Students learn by constructing molar relaxivity curves based on inversion recovery data sets that Magnevist is more relaxive than Dotarem. This experiment is suitable for any analytical chemistry laboratory with access to NMR.

Copper-catalyzed oxidation of azolines to azoles.

We report herein convenient, aerobic conditions for the oxidation of thiazolines to thiazoles and data regarding the oxidation mechanism. These reactions feature operationally simple and environmentally benign conditions and proceed in good yield to afford the corresponding azoles, thus enabling the inexpensive preparation of valuable molecular building blocks. Incorporation of a novel diimine-ligated copper catalyst, [((Mes)DAB(Me))Cu(II)(OH(2))(3)](2+) [(-)OTf](2), provides increased reaction efficiency in many cases. In other cases copper-free conditions involving a stoichiometric quantity of base affords superior results.