Crystal engineering studies: polymorphs and co-crystals

We review the key topics of one of the areas with the biggest impact of the last years in the chemical and pharmaceutical industry that is Crystal Engineering. The relevance of polymorphs and co-crystals from different points of view is been highlighted and broadly illustrated by means of several recent examples of studies carried out in this field. In addition, the most suitableinstrumental techniques and the intellectual property implications are reviewed.

Liquid chromatography - Mass spectrometry

In this article, selected examples of applications of liquid chromatography coupled to mass spectrometry are given. The examples include the analysis of i) impurities in manufactured, pharmaceutical or synthesis products, ii) polyphenols in natural products, and iii) phytohormones in plant extracts. Finally, examples of applications of molecular characterization via flow injection analysis by electron spray ionization mass spectrometry (ESI-MS) are also given.

X-ray single crystal and powder diffraction: possibilities and applications

In this article the main possibilities of single crystal and powder diffraction analysis using conventional laboratory x-ray sources are introduced. Several examples of applications with different solid samples and in different fields of applications are shown illustrating the multidisciplinary capabilities of both techniques.

Fast analysis of doping agents in urine by ultra-high-pressure liquid chromatography-quadrupole time-of-flight mass spectrometry I. Screening analysis.

The general strategy to perform anti-doping analyses of urine samples starts with the screening for a wide range of compounds. This step should be fast, generic and able to detect any sample that may contain a prohibited substance while avoiding false negatives and reducing false positive results. The experiments presented in this work were based on ultra-high-pressure liquid chromatography coupled to hybrid quadrupole time-of-flight mass spectrometry. Thanks to the high sensitivity of the method, urine samples could be diluted 2-fold prior to injection. One hundred and three forbidden substances from various classes (such as stimulants, diuretics, narcotics, anti-estrogens) were analysed on a C(18) reversed-phase column in two gradients of 9min (including two 3min equilibration periods) for positive and negative electrospray ionisation and detected in the MS full scan mode. The automatic identification of analytes was based on retention time and mass accuracy, with an automated tool for peak picking. The method was validated according to the International Standard for Laboratories described in the World Anti-Doping Code and was selective enough to comply with the World Anti-Doping Agency recommendations. In addition, the matrix effect on MS response was measured on all investigated analytes spiked in urine samples. The limits of detection ranged from 1 to 500ng/mL, allowing the identification of all tested compounds in urine. When a sample was reported positive during the screening, a fast additional pre-confirmatory step was performed to reduce the number of confirmatory analyses.

Determination of the Enantiomers of Mianserin and its Metabolites in Plasma by Capillary Electrophoresis After Liquid-Liquid Extraction and On-Column Sample Preconcentration

Capillary electrophoresis has drawn considerable attention in the past few years, particularly in the field of chiral separations because of its high separation efficiency. However, its routine use in therapeutic drug monitoring is hampered by its low sensitivity due to a short optical path. We have developed a capillary zone electrophoresis (CZE) method using 2mM of hydroxypropyl-β-cyclodextrin as a chiral selector, which allows base-to-base separation of the enantiomers of mianserin (MIA), desmethylmianserin (DMIA), and 8-hydroxymianserin (OHMIA). Through the use of an on-column sample concentration step after liquid-liquid extraction from plasma and through the presence of an internal standard, the quantitation limits were found to be 5 ng/mL for each enantiomer of MIA and DMIA and 15 ng/mL for each enantiomer of OHMIA. To our knowledge, this is the first published CE method that allows its use for therapeutic monitoring of antidepressants due to its sensitivity down to the low nanogram range. The variability of the assays, as assessed by the coefficients of variation (CV) measured at two concentrations for each substance, ranged from 2 to 14% for the intraday (eight replicates) and from 5 to 14% for the interday (eight replicates) experiments. The deviations from the theoretical concentrations, which represent the accuracy of the method, were all within 12.5%. A linear response was obtained for all compounds within the range of concentrations used for the calibration curves (10-150 ng/mL for each enantiomer of MIA and DMIA and 20-300 ng/mL for each enantiomer of OHMIA). Good correlations were calculated between [(R) + (S)]-MIA and DMIA concentrations measured in plasma samples of 20 patients by a nonchiral gas chromatography method and CZE, and between the (R)- and (S)-concentrations of MIA and DMIA measured in plasma samples of 37 patients by a previously described chiral high-performance liquid chromatography method and CZE. Finally, no interference was noted from more than 20 other psychotropic drugs. Thus, this method, which is both sensitive and selective, can be routinely used for therapeutic monitoring of the enantiomers of MIA and its metabolites. It could be very useful due to the demonstrated interindividual variability of the stereoselective metabolism of MIA.

Recent Advances in Valorization Methods of Inorganic/Organic Solid, Liquid, and Gas Wastes

The main goal of this special issue was to gather contributions dealing with the latest breakthrough methods for providing value compounds and energy/fuel from waste valorization. Valorization is a relatively new approach in the area of industrial wastes management, a key issue to promote sustainable development. In this field, the recovery of value-added substances, such as antioxidants, proteins, vitamins, and so forth, from the processing of agroindustrial byproducts, is worth mentioning. Another important valorization approach is the use of biogas from waste treatment plants for the production of energy. Several approaches involving physical and chemical processes, thermal and biological processes that ensure reduced emissions and energy consumptions were taken into account. The papers selected for this topical issue represent some of the mostly researched methods that currently promote the valorization of wastes to energy and useful materials ...

Oxygen isotope sector zoning in natural hydrothermal quartz

Oxygen isotope measurements using SIMS and laser-fluorination methods confirm the presence of concentric and sector zoning in low-temperature (200 degrees C to < 400 degrees C) hydrothermal quartz from Alpine veins. While concentric zoning is most readily explained by changes in the chemical composition of the fluid or temperature of crystallization, the reasons for sector zoning are more difficult to explain. Relative enrichment in (18)O for crystallographically different sectors of quartz corresponds to m > r > z. Sector zoning is, however, largely limited to the exterior zones of crystals and/or to crystals with large Al (> 1000 ppm) and trace element contents, probably formed at temperatures < 250 degrees C. Differences in delta(18)O between the prismatic (m) relative to the rhombohedral (r and z) growth sectors of up to 2 parts per thousand can be explained by a combination of a face-related crystallographic and/or a growth rate control. In contrast, isotopic sector zoning of up to about 1.5 parts per thousand amongst the different rhombohedral faces increases in parallel with the trace element content and is likely to represent disequilibrium growth. This is indicated by non-systematic, up to 2 parts per thousand, differences within single growth zones and the irregular, larger or smaller, delta(18)O values (of several permil) of the exterior compared to the inner zones of the same crystals. Disequilibrium growth may be related to the large trace element content incorporated into the growing quartz at lower temperatures (< 250 degrees C) and/or be related to fluid-vapour separation, allowing crystal growth from both a vapour as well as a liquid phase.

Analytical interference of 4-hydroxy-3-methoxymethamphetamine with the measurement of plasma free normetanephrine by ultra-high pressure liquid chromatography-tandem mass spectrometry.

OBJECTIVES: The diagnosis of pheochromocytoma relies on the measurement of plasma free metanephrines assay whose reliability has been considerably improved by ultra-high pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Here we report an analytical interference occurring between 4-hydroxy-3-methoxymethamphetamine (HMMA), a metabolite of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy"), and normetanephrine (NMN) since they share a common pharmacophore resulting in the same product ion after fragmentation. DESIGN AND METHODS: Synthetic HMMA was spiked into plasma samples containing various concentrations of NMN and the intensity of the interference was determined by UPLC-MS/MS before and after improvement of the analytical method. RESULTS: Using a careful adjustment of chromatographic conditions including the change of the UPLC analytical column, we were able to distinguish both compounds. HMMA interference for NMN determination should be seriously considered since MDMA activates the sympathetic nervous system and if confounded with NMN may lead to false-positive tests when performing a differential diagnostic of pheochromocytoma.

Olivine growth-rates in a tholeiitic basalt - an experimental study of melt inclusions in plagioclase

Basaltic glass inclusions trapped in plagioclase phenocrysts (An84) are remnant of their parent magmatic liquid. They can be used as natural reactors for the experimental investigation of olivine growth rate as a function of temperature. The growth of one olivine nucleus can be observed at constant temperature. Supercooling from 15-degrees to 150-degrees-C have been investigated. Growth habits vary from equant to feather in qualitative agreement with previous studies. Growth rates vary from < 10(-10) m s-1 to 6.10(-7) m s-1; they vary with the direction, the growth process (planar or dendritic) and the degree of supercooling. Chemical analysis of crystal overgrowth and the remaining liquid composition enables a mass-balance calculation which confirms the rates determined optically. The small number of results obtained so far does not permit to draw inferences on the growth mechanisms.

High-throughput and sensitive quantitation of plasma catecholamines by ultraperformance liquid chromatography-tandem mass spectrometry using a solid phase microwell extraction plate.

Plasma catecholamines provide a reliable biomarker of sympathetic activity. The low circulating concentrations of catecholamines and analytical interferences require tedious sample preparation and long chromatographic runs to ensure their accurate quantification by HPLC with electrochemical detection. Published or commercially available methods relying on solid phase extraction technology lack sensitivity or require derivatization of catecholamine by hazardous reagents prior to tandem mass spectrometry (MS) analysis. Here, we manufactured a novel 96-well microplate device specifically designed to extract plasma catecholamines prior to their quantification by a new and highly sensitive ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. Processing time, which included sample purification on activated aluminum oxide and elution, is less than 1 h per 96-well microplate. The UPLC-MS/MS analysis run time is 2.0 min per sample. This UPLC-MS/MS method does not require a derivatization step, reduces the turnaround time by 10-fold compared to conventional methods used for routine application, and allows catecholamine quantification in reduced plasma sample volumes (50-250 μL, e.g., from children and mice).

Si3N4 single-crystal nanowires grown from silicon micro- and nanoparticles near the threshold of passive oxidation

A simple and most promising oxide-assisted catalyst-free method is used to prepare silicon nitride nanowires that give rise to high yield in a short time. After a brief analysis of the state of the art, we reveal the crucial role played by the oxygen partial pressure: when oxygen partial pressure is slightly below the threshold of passive oxidation, a high yield inhibiting the formation of any silica layer covering the nanowires occurs and thanks to the synthesis temperature one can control nanowire dimensions

Reduction of Concrete Deterioration by Ettringite Using Crystal Growth Inhibition Techniques: Part II Field Evaluation of Inhibitor Effectiveness, TR-469, 2004

The effects of diethylenetriaminpenta(methylenephosphonic acid) (DTPMP), a phosphonate inhibitor, on the growth of delayed ettringite have been evaluated using concrete in highway US 20 near Williams, Iowa, and the cores of six highways subject to moderate (built in 1992) or minor (built in 1997) deterioration. Application of 0.01 and 0.1 vol. % DTPMP to cores was made on a weekly or monthly basis for one year under controlled laboratory-based freeze-thaw and wet-dry conditions over a temperature range of -15 degrees to 58 degrees C to mimic extremes in Iowa roadway conditions. The same concentrations of phosphonate were also applied to cores left outside (roof of Science I at Iowa State University) over the same period of time. Nineteen applications of 0.1 vol. % DTPMP with added deicing salt solution (about 23 weight % NACL) were made to US 20 during the winters of 2003 and 2004. In untreated samples, air voids, pores, and occasional cracks are lined with acicular ettringite crystals (up to 50 micrometers in length) whereas air voids, pores, and cracks in concrete from the westbound lane of US 20 are devoid of ettringite up to a depth of about 0.5 mm from the surface of the concrete. Ettringite is also absent in zones up to 6 mm from the surface of concrete slabs placed on the roof of Science I and cores subject to laboratory-based freeze-thaw experiments. In these zones, the relatively high concentration of DTPMP caused it to behave as a chelator. Stunted ettringite crystals 5 to 25 micrometers in length, occasionally coated with porlandite, form on the margins of these zones indicating that in these areas DTPMP behaved as an inhibitor due to a reduction in the concentration of phosphonate. Analyses of mixes of ettringite and DTPMP using electrospray mass spectrometry suggests that the stunting of ettringite growth is caused by the adsorption of a Ca2+ ion and a water molecule to deprotonated DTPMP on the surface of the {0001} face of ettringite. It is anticipated that by using a DTPMP concentration of between 0.001 and 0.01 vol. % for the extended life of a highway (i.e. >20 years), deterioration caused by the expansive growth of ettringite will be markedly reduced.

Alveolar epithelial CNGA1 channels mediate cGMP-stimulated, amiloride-insensitive, lung liquid absorption.

Impairment of lung liquid absorption can lead to severe respiratory symptoms, such as those observed in pulmonary oedema. In the adult lung, liquid absorption is driven by cation transport through two pathways: a well-established amiloride-sensitive Na(+) channel (ENaC) and, more controversially, an amiloride-insensitive channel that may belong to the cyclic nucleotide-gated (CNG) channel family. Here, we show robust CNGA1 (but not CNGA2 or CNGA3) channel expression principally in rat alveolar type I cells; CNGA3 was expressed in ciliated airway epithelial cells. Using a rat in situ lung liquid clearance assay, CNG channel activation with 1 mM 8Br-cGMP resulted in an approximate 1.8-fold stimulation of lung liquid absorption. There was no stimulation by 8Br-cGMP when applied in the presence of either 100 μM L: -cis-diltiazem or 100 nM pseudechetoxin (PsTx), a specific inhibitor of CNGA1 channels. Channel specificity of PsTx and amiloride was confirmed by patch clamp experiments showing that CNGA1 channels in HEK 293 cells were not inhibited by 100 μM amiloride and that recombinant αβγ-ENaC were not inhibited by 100 nM PsTx. Importantly, 8Br-cGMP stimulated lung liquid absorption in situ, even in the presence of 50 μM amiloride. Furthermore, neither L: -cis-diltiazem nor PsTx affected the β(2)-adrenoceptor agonist-stimulated lung liquid absorption, but, as expected, amiloride completely ablated it. Thus, transport through alveolar CNGA1 channels, located in type I cells, underlies the amiloride-insensitive component of lung liquid reabsorption. Furthermore, our in situ data highlight the potential of CNGA1 as a novel therapeutic target for the treatment of diseases characterised by lung liquid overload.

Short-term stability of testosterone and epitestosterone conjugates in urine samples: quantification by liquid chromatography-linear ion trap mass spectrometry.

A simple method using liquid chromatography-linear ion trap mass spectrometry for simultaneous determination of testosterone glucuronide (TG), testosterone sulfate (TS), epitestosterone glucuronide (EG) and epitestosterone sulfate (ES) in urine samples was developed. For validation purposes, a urine containing no detectable amount of TG, TS and EG was selected and fortified with steroid conjugate standards. Quantification was performed using deuterated testosterone conjugates to correct for ion suppression/enhancement during ESI. Assay validation was performed in terms of lower limit of detection (1-3ng/mL), recovery (89-101%), intraday precision (2.0-6.8%), interday precision (3.4-9.6%) and accuracy (101-103%). Application of the method to short-term stability testing of urine samples at temperature ranging from 4 to 37 degrees C during a time-storage of a week lead to the conclusion that addition of sodium azide (10mg/mL) is required for preservation of the analytes.