Nanostructure of Gasification Charcoal (Biochar).

In this work, we investigate the molecular composition and nanostructure of gasification charcoal (biochar) by comparing it with heat-treated fullerene arc-soot. Using ultrahigh resolution Fourier transform ion-cyclotron resonance and laser desorption ionization time-of-flight mass spectrometry, Raman spectroscopy, and high resolution transmission electron microscopy we analyzed charcoal of low tar content obtained from gasification. Mass spectrometry revealed no magic number fullerenes such as C60 or C70 in the charcoal. The positive molecular ion m/ z 701, previously considered a graphitic part of the nanostructure, was found to be a breakdown product of pyrolysis and not part of the nanostructure. A higher mass distribution of ions similar to that found in thermally treated fullerene soot indicates that they share a nanostructure. Recent insights into the formation of all carbon fullerenes reveal that conditions in charcoal formation are not optimal for the formation of fullerenes, but instead, curved carbon structures coalesce into fulleroid-like structures. Microscopy and spectroscopy support such a stacked, fulleroid-like nanostructure, which was explored using reactive molecular dynamics simulations

A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR – implications for therapeutic failure and drug resistance

<p>Abstract</p> <p>Background</p> <p>Counterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).</p> <p>Methods</p> <p>In 2003, 'mystery' shoppers were asked to buy artesunate tablets from 180 outlets in 12 of the 18 Lao provinces. Outlets were selected using stratified random sampling by investigators not involved in sampling. Samples were analysed for packaging characteristics, by the Fast Red Dye test, high-performance liquid chromatography (HPLC), mass spectrometry (MS), X-ray diffractometry and pollen analysis.</p> <p>Results</p> <p>Of 180 outlets sampled, 25 (13.9%) sold oral artesunate. Outlets selling artesunate were more commonly found in the more malarious southern Laos. Of the 25 outlets, 22 (88%; 95%CI 68–97%) sold counterfeit artesunate, as defined by packaging and chemistry. No artesunate was detected in the counterfeits by any of the chemical analysis techniques and analysis of the packaging demonstrated seven different counterfeit types. There was complete agreement between the Fast Red dye test, HPLC and MS analysis. A wide variety of wrong active ingredients were found by MS. Of great concern, 4/27 (14.8%) fakes contained detectable amounts of artemisinin (0.26–115.7 mg/tablet).</p> <p>Conclusion</p> <p>This random survey confirms results from previous convenience surveys that counterfeit artesunate is a severe public health problem. The presence of artemisinin in counterfeits may encourage malaria resistance to artemisinin derivatives. With increasing accessibility of artemisinin-derivative combination therapy (ACT) in Laos, the removal of artesunate monotherapy from pharmacies may be an effective intervention.</p

A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia

Paul Newton and colleagues' international, collaborative study found evidence that counterfeit artesunate was being manufactured in China, which prompted a criminal investigation

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

BACKGROUND: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. METHODS: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. RESULTS: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems

Ambient ionization mass spectrometry for the forensic screening of pharmaceuticals and the determination of potential drug candidates

Ambient mass spectrometry (MS) is a new and growing sub-field in MS which has opened new research avenues, particularly for applications relating to the analysis of solid samples. Results on the implementation and application of ambient MS techniques including: desorption electrospray ionization (DESI) and direct analysis in real time (DART) indicated that these techniques could serve as complementary tools for the rapid qualitative screening of pharmaceuticals, allowing up to two orders of magnitude improvement in throughput compared to traditional methods such as liquid chromatography MS. The selectivity of DESI could be enhanced by performing the experiment in the reactive mode. In this mode, complexation reactions between reagents added to the spray solvent and analytes on the sample surface resulted in analyte stabilization, inhibiting fragmentation. They also resulted in a concomitant enhancement in the analyte surface activity, facilitating their evaporation from secondary droplets culminating in an improvement in sensitivity. Also for drug tablets analysis, the analyte signal dependency on DESI geometrical set-up variables could be mitigated following the careful and controlled addition of an isotopically labeled internal standard (IS) to the sample or by spraying samples with a pair of reagents with different affinities for the analyte. Either of these approaches resulted in an analyte-to-IS signal ratio (in the former) or an analyte complex ratio (in the later), which was largely independent of DESI experimental variables allowing quantitative analysis using this technique. DESI MS was also observed to be a very powerful tool for determining the 2-D distribution of various pharmaceutically important compounds on tablet and tissue surfaces. The ability to map the distribution of molecules of interest by DESI MS has very great implications in drug tablet quality control and in determining the role of chemical signals presented on tissue surfaces. DESI was observed to be limited to ionizing molecules of medium to high polarities without much limitation in terms of mass range, whereas DART was better suited for the analysis of molecules within a broader range of polarities, but within a more limited mass range (up to 800 Da approximately). These limitations were circumvented by implementing a novel multimode ambient ion source, desorption electrospray/metastable-induced ionization (DEMI), which combines various aspects of DESI and DART. Initial experiments with the DEMI ion source demonstrated its ability to enable the simultaneous analysis of molecules within a broader range of polarities and masses than DESI and DART alone.Ph.D.Committee Chair: Fernández, Facundo; Committee Member: Bottomley, Lawrence; Committee Member: Mizaikoff, Boris; Committee Member: Orlando, Thomas; Committee Member: Prausnitz, Mar

Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization

Presented here is a novel ambient ion source termed infrared laser ablation metastable-induced chemical ionization (IR-LAMICI). IR-LAMICI integrates IR laser ablation and direct analysis in real time (DART)-type metastable-induced chemical ionization for open air mass spectrometry (MS) ionization. The ion generation in the IR-LAMICI source is a two step process. First, IR laser pulses impinge the sample surface ablating surface material. Second, a portion of ablated material reacts with the metastable reactive plume facilitating gas-phase chemical ionization of analyte molecules generating protonated or deprotonated species in positive and negative ion modes, respectively. The successful coupling of IR-laser ablation with metastable-induced chemical ionization resulted in an ambient plasma-based spatially resolved small molecule imaging platform for mass spectrometry (MS). The analytical capabilities of IR-LAMICI are explored by imaging pharmaceutical tablets, screening counterfeit drugs, and probing algal tissue surfaces for natural products. The resolution of a chemical image is determined by the crater size produced with each laser pulse but not by the size of the metastable gas jet. The detection limits for an active pharmaceutical ingredient (acetaminophen) using the IR-LAMICI source is calculated to be low picograms. Furthermore, three-dimensional computational fluid dynamic simulations showed improvements in the IR-LAMICI ion source are possible. © 2010 American Chemical Society

Transmission Geometry Laser Desorption Atmospheric Pressure Photochemical Ionization Mass Spectrometry for Analysis of Complex Organic Mixtures

We present laser desorption atmospheric pressure photochemical ionization mass spectrometry (LD/APPCI MS) for rapid throughput analysis of complex organic mixtures, without the need for matrix, electric discharge, secondary electrospray, or solvents/vaporizers. Analytes dried on a microscope slide are vaporized in transmission geometry by a laser beam aligned with the atmospheric pressure inlet of the mass spectrometer. The laser beam initiates a cascade of reactions in the region between the glass slide and MS inlet, leading to generation of reagent ions for chemical ionization of vaporized analyte. Positive analyte ions are generated predominantly by proton transfer, charge exchange, and hydride abstraction, whereas negative ions are generated by electron capture or proton transfer reactions, enabling simultaneous analysis of saturated, unsaturated, and heteroatom-containing hydrocarbons. The absence of matrix interference renders LD/APPCI MS particularly useful for analysis of small molecules (<2000 Da) such as those present in petroleum crude oil and petroleum deposits. [M + H]⁺ and M^+• dominate the positive-ion mass spectra for olefins and polyaromatic hydrocarbons, whereas saturated hydrocarbons are observed mainly as [M – H]⁺ and/or M^+•. Heteroatom-containing hydrocarbons are observed predominantly as [M + H]⁺. [M – H]⁻ and M^–• are the dominant negative ions observed for analytes of lower gas-phase basicity or higher electron affinity than O₂. The source was coupled with a 9.4 T Fourier transform ion cyclotron resonance mass spectrometer (FTICR MS) to resolve and identify thousands of peaks from Athabasca bitumen heavy vacuum gas oil distillates (400–425 and 500–538 °C), enabling simultaneous characterization of their polar and nonpolar composition. We also applied LD/APPCI FTICR MS for rapid analysis of sodium and calcium naphthenate deposits with little to no sample pretreatment to provide mass spectral fingerprints that enable reliable compositional characterization

High-Field Orbitrap Mass Spectrometry and Tandem Mass Spectrometry for Molecular Characterization of Asphaltenes

This work introduces a novel approach by use of high-energy collision-induced dissociation for fragmenting asphaltenes into their constituent stable aromatic cores as a means for determining the relative proportions of island-to-archipelago structures. This approach is particularly useful for comparing asphaltenes from various crude oils. Ion generation from asphaltenes was performed by use of atmospheric pressure photoionization, which has been demonstrated to provide hydrogen-to-carbon ratios consistent with bulk measurements by combustion analysis with less than 10% relative error. The fragmentation behavior of asphaltenes was first evaluated with model compounds consisting of island and archipelago structures by use of low- and high-energy collision-induced dissociation (CID and HCD). Unlike CID, HCD enables dissociation of model compounds to their stable aromatic cores. This allows facile classification as either island or archipelago on the basis of the discrepancy in the double-bond equivalents between the precursors and stable aromatic cores. Model compound studies also showed that when HCD is utilized for the simultaneous dissociation of multiple precursor ions, efficient fragmentation of all precursors only occurs when ions within a narrow mass window are presented for analysis. The HCD approach was then applied to characterize narrow mass segments of crude oil asphaltenes, including those derived from hydrotreated resids. Observed island-to-archipelago proportions were consistent with the chemical transformations that occur during the hydrotreating process. Importantly, the method also demonstrates that the proportion of island-to-archipelago structures in asphaltenes decreases with increase molecular weight