Systematic comparison of δ13C measurements of testosterone and derivative steroids in a freeze-dried urine candidate reference material for sports drug testing by gas chromatography/combustion/isotope ratio mass spectrometry and uncertainty evaluation using four different metrological approaches

An alternative calibration procedure for use when performing carbon isotope ratio measurements by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) has been developed. This calibration procedure does not rely on the corrections in-built in the instrument software, as the carbon isotope ratios of a sample are calculated from the measured raw peak areas. The method was developed for the certification of a urine reference material for sports drug testing, as the estimation of measurement uncertainty is greatly simplified. To ensure that the method is free from bias arising from the choice of calibration material and instrument, the carbon isotope ratios of steroids in urine extracts were measured using two different instruments in different laboratories, and three different reference materials (CU/USADA steroid standards from Brenna Laboratory, Cornell University; NIST RM8539 mineral oil; methane calibrated against NIST RM8560 natural gas). The measurements were performed at LGC and the Australian National Measurement Institute (NMI). It was found that there was no significant difference in measurement results when different instruments and reference materials were used to measure the carbon isotope ratio of the major testosterone metabolites androsterone and etiocholanolone, or the endogenous reference compounds pregnanediol, 11- ketoetiocholanolone and 11β-hydroxyandrosterone. Expanded measurement uncertainties at the 95% coverage probability ranged from 0.21‰ to 1.4‰, depending on analyte, instrument and reference material. The measurement results of this comparison were used to estimate a measurement uncertainty of δ(13)C for the certification of the urine reference material being performed on a single instrument using a single reference material at NMI.     

Fast determination of oleic acid in pork by flow injection analysis/mass spectrometry

In some Mediterranean products such as olive oil or ham, oleic acid is the most abundant component of the total fat. Due to the large volume of trade in these products, it may be necessary to analyze oleic fatty acids in high numbers of samples in short periods of time. However, using classic lipid analysis techniques, it is not always possible to cope with these high demands. To solve this problem, a high-throughput analytical method for oleic fatty acid quantification in pork is presented. The purpose of the method is to avoid liquid chromatography processes using a flow injection analysis (FIA) system based on electrospray ionization mass spectrometry. The use of pentadecanoic fatty acid as an internal standard overcame matrix effects. The oleic FIA technique could be used as a suitable method for discriminating carcass samples for selection and labeling by oleic acid content when large numbers of pork samples must be processed in a short period of time.     

Synthesis and Kinetic Study of Hydroxy/Fluoroapatite Solid Solution Formation by Decomposition of a Ca‐EDTA Complex

Fluoroapatite/hydroxyapatite (FA/HA) solid solutions were synthesized through the decomposition of a Ca(EDTA) complex in presence of phosphate and fluoride ions. Fluorine content and morphology depend on initial pH value. Phase identification, fluorine content, crystallinity and morphology of the obtained products were studied via chemical analysis, FTIR, SEM, XRD, and EDS. The kinetic study shows a catalytic dependence on pH value. The values of k₀, k_H+ and k_OH are reported.     

Exploring BODIPY Derivatives as Singlet Oxygen Photosensitizers for PDT

This minireview is devoted to honoring the memory of Dr. Thomas Dougherty, a pioneer of modern photodynamic therapy (PDT). It compiles the most important inputs made by our research group since 2012 in the development of new photosensitizers based on BODIPY chromophore which, thanks to the rich BODIPY chemistry, allows a finely tuned design of the photophysical properties of this family of dyes to serve as efficient photosensitizers for the generation of singlet oxygen. These two factors, photophysical tuning and workable chemistry, have turned BODIPY chromophore as one of the most promising dyes for the development of improved photosensitizers for PDT. In this line, this minireview is mainly related to the establishment of chemical methods and structural designs for enabling efficient singlet oxygen generation in BODIPYs. The approaches include the incorporation of heavy atoms, such as halogens (iodine or bromine) in different number and positions on the BODIPY scaffold, and also transition metal atoms, by their complexation with Ir(III) center, for instance. On the other hand, low-toxicity approaches, without involving heavy metals, have been developed by preparing several orthogonal BODIPY dimers with different substitution patterns. The advantages and drawbacks of all these diverse molecular designs based on BODIPY structural framework are described.     

The NSAIDs Indomethacin and Diflunisal as Scavengers of Photogenerated Reactive Oxygen Species

Diflunisal (DFNS) and Indomethacin (IMTC) are two profusely employed NSAIDs that provide anti‐inflammatory and analgesic effects in humans. The scavenging of reactive oxygen species (ROS) by both NSAIDs was systematically studied in pH 7 aqueous solution. The ROS O₂(¹Δ_g), O₂^?? and H₂O₂, generated by visible light irradiation of Riboflavin (Rf) in the presence of DFNS and IMTC, are deactivated by the NSAIDs. The ROS scavenging action by both NSAIDs constitutes an interesting result and adds one more positive aspect to the beneficial actions attributed to these drugs. Nevertheless it should be taken into account that several NSAIDs, in particular IMTC, have been connected to the pathogenesis of gastric mucosal lesions, which in some cases includes ROS generating‐ability. DFNS quenches ROS in a dominant physical fashion. It constitutes an excellent protective‐antioxidant provided that is practically not destroyed/oxidized after the ROS scavenging action. IMTC, being also an efficient interceptor of ROS, belong to the so‐called group of sacrificial‐ROS quenchers: It is easily degraded by the oxidative species in the scavenging action. Although this property is negative in the context of prolonged ROS elimination, exhibits a promissory aspect for the degradation of pharmaceutical contaminants, such as NSAIDs, in waste waters.     

Self‐Sorting of Cyclic Peptide Homodimers into a Heterodimeric Assembly Featuring an Efficient Photoinduced Intramolecular Electron‐Transfer Process

We describe the thermodynamic characterisation of the self‐sorting process experienced by two homodimers assembled by hydrogen‐bonding interactions through their cyclopeptide scaffolds and decorated with Zn–porphyrin and fullerene units into a heterodimeric assembly that contains one electron‐donor (Zn–porphyrin) and one electron‐acceptor group (fullerene). The fluorescence of the Zn–porphyrin unit is strongly quenched upon heterodimer formation. This phenomenon is demonstrated to be the result of an efficient photoinduced electron‐transfer (PET) process occurring between the Zn–porphyrin and the fullerene units of the heterodimeric system. The recombination lifetime of the charge‐separated state of the heterodimer complex is in the order of 180 ns. In solution, both homo‐ and heterodimers are present as a mixture of three regioisomers: two staggered and one eclipsed. At the concentration used for this study, the high stability constant determined for the heterodimer suggests that the eclipsed conformer is the main component in solution. The application of the bound‐state scenario allowed us to calculate that the heterodimer exists mainly as the eclipsed regioisomer (75–90 %). The attractive interaction that exists between the donor and acceptor chromophores in the heterodimeric assembly favours their arrangement in close contact. This is confirmed by the presence of charge‐transfer bands centred at 720 nm in the absorption spectrum of the heterodimer. PET occurs in approximately 75 % of the chromophores after excitation of both Zn–porphyrin and fullerene chromophores. Conversely, analogous systems, reported previously, decorated with extended tetrathiafulvalene and fullerene units showed a PET process in a significantly reduced extent (33 %). We conclude that the strength (stability constant (K)×effective molarity (EM)) of the intramolecular interaction established between the two chromophores in the Zn–porphyrin/fullerene cyclopeptide‐based heterodimers controls the regioisomeric distribution and regulates the high extent to which the PET process takes place in this system.     

A simple method for simultaneous determination of nine triazines in drinking water

A simple, effective, and economic method for determination of nine triazines (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine, and terbutryn) in drinking water based on solid-phase extraction (SPE) followed by high-performance liquid chromatography-diode array detection (HPLC-DAD) was developed. A specialized solid phase (Oasis HLB) was used, and the parameters that may affect the efficiency of SPE were optimized. The limits of detection (ranged from 0.010 to 0.023 µg L^?1) were satisfactory and allow the determination of triazines at the levels required by European Union legislation. Repeatability (2.4–7.6%) and intermediate precision (0.9–11.0%) calculated at 0.1 µg L^?1 (legislation level) were adequate. The accuracy calculated as the average recovery of spiked tap and mineral waters was higher than 86% for all compounds. The developed method also could be used for undergraduate laboratory experiments because it acquaints students with solution preparation, solid phase extraction procedure, and HPLC-DAD technique.     

Application of laser ablation multicollector inductively coupled plasma mass spectrometry for the measurement of calcium and lead isotope ratios in packaging for discriminatory purposes

The potential of high‐precision calcium and lead isotope ratio measurements using laser ablation coupled to multicollector inductively coupled plasma mass spectrometry (LA‐MC‐ICP‐MS) to aid distinction between four genuine and five counterfeit pharmaceutical packaging samples and further classification of counterfeit packaging samples has been evaluated. We highlight the lack of reference materials for LA‐MC‐ICP‐MS isotope ratio measurements in solids. In this case the problem is minimised by using National Institute of Standards and Technology Standard Reference Material (NIST SRM) 915a calcium carbonate (as solid pellets) and NIST SRM610 glass disc for sample bracketing external standardisation. In addition, a new reference material, NIST SRM915b calcium carbonate, has been characterised in‐house for Ca isotope ratios and is used as a reference sample. Significant differences have been found between genuine and counterfeit samples; the method allows detection of counterfeits and aids further classification of packaging samples. Typical expanded uncertainties for measured‐corrected Ca isotope ratio values (⁴³Ca/⁴⁴Ca and ⁴²Ca/⁴⁴Ca) were found to be below 0.06% (k = 2, 95% confidence) and below 0.2% for measured‐corrected Pb isotope ratios (²⁰⁷Pb/²⁰⁶Pb and ²⁰⁸Pb/²⁰⁶Pb). This is the first time that Ca isotope ratios have been measured in packaging materials using LA coupled to a multicollector (MC)‐ICP‐MS instrument. The use of LA‐MC‐ICP‐MS for direct measurement of Ca and Pb isotopic variations in cardboard/ink in packaging has definitive potential to aid counterfeit detection and classification. Copyright © 2010 John Wiley & Sons, Ltd.     

Background electrolytes in 50% methanol/water for the determination of acidity constants of basic drugs by capillary zone electrophoresis

The acidic dissociation constants of several hydrophobic drugs, amiodarone and a series of antidepressants that show a secondary or tertiary amino group, were determined in a 50% methanol/water mixture by capillary zone electrophoresis. The electrophoretic behavior of buffers prepared from sodium acetate, tris(hydroxymethyl) aminomethane hydrochloride, sodium hydrogenphosphate, ammonium chloride, ethanolamine, butilammonium chloride, and sodium borate in the hydroalcoholic solution was tested. Thus, all of them follow the Ohm's law until about 25 kV and, therefore, they can be used without significant Joule heat dissipation at 20 kV. For the studied drugs, buffers prepared with phosphate or borate give effective mobility measurements lower than those from other buffers. The wide pKa range of the studied drugs provides a wide pH range where the protonated forms of the amino compounds coexist with hydrogenphosphate ions and where the neutral amines coexist with boric acid. The decrease of the experimental effective mobilities in these instances can be explained through the interactions between coexisting species. Therefore, phosphate and borate buffers should be avoided to determine the mobility of amines with aqueous pKa higher than 8, at least in solutions with high methanol content. Independent measurements of acidic dissociation constants of drugs validate this statement.