Search

Both new guidelines concerning elemental impurity limit concentrations and novel analytical procedures for elemental analysis of pharmaceutical substances are being adopted by the United States Pharmacopeia (USP). This paper outlines the optimization of two sample preparation procedures for organic pharmaceutical excipient products, one relying on direct dissolution in an aqueous medium and another on microwave-assisted acid digestion. Optimization particularly involved the stabilization and reliable determination of Hg, Pd and Os. Analyte concentrations and spike recoveries were determined in two organic pharmaceutical excipients using a quadrupole ICP-MS instrument equipped with a collision–reaction cell. Aqueous dissolution was achieved with 0.009 mM KBrO3 in 1% (v/v) HNO3 and 1% (v/v) HCl and microwave-assisted acid digestion was performed with aqua regia. Polyatomic interferences originally hampering the accurate determination of 51V, 52Cr, 53Cr, 55Mn, 56Fe and 75As were eliminated through introduction of He/H2 collision–reaction gas at a flow rate of 4.5–5.1 ml min−1 and applying a kinetic energy barrier of 3 V between the hexapole collision–reaction cell and the quadrupole analyzer. Limits of detection were more than a factor of ten lower than the proposed limit concentrations for parenteral administration and the impurity concentrations in the products tested never exceeded the limit concentrations defined by USP. Elemental spike recoveries ranged between 93.8 and 109.9% when standard addition was used for calibration, with relative standard deviations (RSDs) ≤12.7%. It is expected that the proposed procedures can be directly implemented for routine impurity analysis of a broad spectrum of pharmaceutical substances. [ABSTRACT FROM AUTHOR]

Abstract: Experiments modeling abiotic methylation of mercury were performed by using methylcobalamin, methyltin, acetic acid and dimethylsulfoxide as the methyl donor compounds. Mercury isotope ratios were measured by using multicollector ICP-MS for both methylmercury and parent inorganic Hg(II). Abiotic methylation of mercury in the dark was accompanied by mass-dependent Hg isotope fractionation with isotope fractionation factors, α product/substrate, ranging from 0.9985 to 0.9995 in terms of δ 202/198Hg values and with undetectable Hg isotope anomalies. The radical substitution reactions, releasing a methyl radical in solution in the dark, facilitated formation of methylmercury and increased the magnitude of the concomitant mass-dependent Hg isotope effect but were not capable of producing any measurable mass-independent anomaly in the isotopic composition of mercury. In contrast to methylation in the dark, photochemical methylation of mercury was accompanied by both mass-dependent and mass-independent Hg isotope fractionation. The latter resulted in selective enrichment of 199Hg and 201Hg isotopes in methylmercury and was attributed to the magnetic isotope effect. These data highlight the fact that the light-assisted methylation of mercury produces a unique mass-independent Hg isotope signature that can be used in tracing the origin of this highly toxic compound. [Copyright &y& Elsevier]

This article overviews recent developments in the use of multicollector inductively coupled plasma mass spectrometry (MC-ICPMS) in studies of mass-independent isotope chemistry of heavy elements. Origins of mass-independent isotope effects and their relevance to isotope ratio measurements by MC-ICPMS are briefly described. The extent to which these effects can affect instrumental mass bias in MC-ICPMS is critically discussed on the basis of the experimental observations. Furthermore, key findings reported in studies of mass-independent isotope fractionation (MIF) of mercury in the field of environmental sciences are reviewed. MIF of heavy elements is not only of interest from a fundamental point of view, but also provides scientists with a new and effective means of studying the biogeochemistry of these elements. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Studies the determination of platinum and rhodium in environmental matrixes by solid sampling-electrothermal vaporization in combination with inductively coupled plasma mass spectrometry. Avoidance of spectral interference; Alleviation of matrix-induced analyte signal suppression during the actual vaporization step; Method of calibration.

The feasibility of elemental fingerprinting in the classification of wines according to their provenance vineyard soil was investigated in the relatively small geographical area of a single wine district. Results for the Stellenbosch wine district (Western Cape Wine Region, South Africa), comprising an area of less than 1000 km2, suggest that classification of wines from different estates (120 wines from 23 estates) is indeed possible using accurate elemental data and multivariate statistical analysis based on a combination of principal component analysis, cluster analysis, and discriminant analysis. This is the first study to demonstrate the successful classification of wines at estate level in a single wine district in South Africa. The elements B, Ba, Cs, Cu, Mg, Rb, Sr, Tl and Zn were identified as suitable indicators. White and red wines were grouped in separate data sets to allow successful classification of wines. Correlation between wine classification and soil type distributions in the area was observed. [ABSTRACT FROM AUTHOR]

Abstract: Prefilled syringes are of increasing importance on the drug product market. Drug products supplied in prefilled syringes have to comply with guidelines on elemental impurity limit concentrations. Elemental impurities may be introduced through any reagents or catalysts used or any product contact surface. This work addresses the determination of elemental impurities leaching from three types of glass syringe container-closure systems supplied by two leading manufacturers. Leachate solutions of every type of syringe were analyzed for Na, Al, Si, W and the 16 elements listed in draft USP chapter 232, which were selected on grounds of toxicity. Elemental impurity concentrations were determined using sector field ICP-mass spectrometry. Significant concentrations of Na and Si were found in all leachate solutions, up to 1200 and 4500μgL−1, respectively. In addition, also Al, As and W were leached out of syringes from one manufacturer in variable amounts, giving rise to average concentrations (std. dev., n =6) of 400 (120), 0.55 (0.08) and 230 (220)μgL−1, respectively. So far, no exceeding of limit concentrations was observed. [Copyright &y& Elsevier]

The correlation between the 11B/10B ratio in grapevine leaves and that in the growth medium was established in a series of hydroponic experiments with grapevine cuttings for different cultivar/rootstocks combinations. The hydroponic growth medium was alternately spiked with boric acid containing B with natural isotope composition and B enriched in 10B, so as to vary the 11B/10B ratio. B isotope ratios in grapevine leaves were determined by quadrupole-based ICP-MS after digestion and complete matrix removal through microwave digestion and isolation of matrix-free B species using ion exchange separation. It was found that the B isotope ratios in the leaves were not identical to those in the growth medium, but that a change in the ratio in the growth medium induced a similar change in the leaves. For a particular cultivar/rootstock combination, a characteristic B isotope ratio was found that was different from the ratio in a group of plants with a different cultivar/rootstock combination. [ABSTRACT FROM AUTHOR]

Abstract: Since considerable time, isotopic analysis of different elements present in a sample, material or object (such as the ‘light’ elements H, C, N, O and S and ‘heavy’ elements, such as Sr and Pb), has been used in provenancing studies, as several factors — defined by “the environment” or origin of the sample — can lead to measurable differences in their isotopic composition. For the light elements, traditionally, (gas source) isotope ratio mass spectrometry (IR-MS) is used, while for a long period of time, thermal ionization mass spectrometry (TIMS) was considered as the only technique capable of detecting subtle variations in the isotopic composition of the ‘heavier’ elements. However, since the introduction of the first inductively coupled plasma mass spectrometers (ICP-MS), considerable attention has been devoted to the development of methodologies and strategies to perform isotopic analysis by means of ICP-MS. While the relatively modest isotope ratio precision offered by single-collector ICP-MS may already be fit-for-purpose under some circumstances, especially the introduction of multi-collector ICP-MS instruments, equipped with an array of Faraday detectors instead of a single electron multiplier, has lead to tremendous improvements in the field of isotopic analysis. As a result, MC-ICP-MS can be seen as a very strong competitor of TIMS nowadays, while it even provides information on the small isotopic variations shown by some elements, that are not or hardly accessible by means of TIMS (e.g., elements with a high ionization energy). Owing to these new instrumental developments, the application field of isotopic analysis by means of ICP-MS is continuously growing, also in the field of provenance determination. This paper is intended as a review of the developments in and the recent applications of isotopic analysis by means of ICP-MS in this specific research field. [ABSTRACT FROM AUTHOR]

Laboratory experiments, modeling the methylation of inorganic Sn(II) by methylcobalamin and the decomposition of methyltin under irradiation with UV light in aqueous solution, have been performed. Methyltin has been separated from inorganic Sn using anion-exchange chromatography and subjected to Sn isotope ratio measurements via solution nebulization multicollector inductively coupled plasma mass spectrometry (MC-ICPMS). The methylation of Sn(II) in the dark was accompanied by mass-dependent Sn isotopic fractionation, which resulted in preferential partitioning of the lighter Sn isotopes into the organic phase, with a shift of ∼0.57 ± 0.12‰ in terms of δ124/116Sn between methylated and inorganic Sn. The methylation of Sn(II) by methylcobalamin under UV irradiation resulted in the accelerated formation of methyltin in the beginning of the process, but was followed by the photolytic degradation of methyltin until its complete mineralization. The photolytic degradation of methyltin in the presence of methylcobalamin and inorganic Sn(II) was slower than that of pure solutions of commercially obtained monomethyltin. This is attributed to the methylating action of methyl radicals produced from photolytically decomposing methylcobalamin. Both synthesis and decomposition of methyltin under UV irradiation were accompanied by both mass-dependent and mass-independent Sn isotopic fractionation, with the latter due to the magnetic isotope effect As a result of this, the lighter Sn isotopes preferentially partition into reaction products, while the odd isotopes, 117Sn and 119Sn, are selectively enriched relative to the other isotopes in the starting molecules. The extent of the observed variations in the isotopic composition of Sn is larger than that documented previously for geological and archeological samples. These results indicate that Sn isotopic fractionation between various chemical forms of Sn in the natural aquatic systems may be significant and can provide new insights into the biogeochemical cycling of the element. [ABSTRACT FROM AUTHOR]

In spite of the advantages that the direct analysis of inorganic samples by means of solid sampling-electrothermal vaporization-inductively coupled plasma mass spectrometry (SS-ETV-ICPMS) may offer, especially in terms of sample throughput, most works until date have only dealt with less complicated organic matrices. This paper reports on the direct determination of seven elements (Al, Mg, Mn, Ni, Sb, Ti and Zr, with concentrations ranging between 0.6 and 150 μg/g) in a thermographic material. This is a challenging application and can be used to assess the real possibilities of SS-ETV-ICPMS for the analysis of inorganic samples. In order to cope with the complex composition of the matrix (Ag, Si and organic compounds), as well as with the different characteristics of the analytes, several approaches and chemical modifiers (HF, HCl, HNO3 and CH3Li) were studied. Finally, two different strategies were optimized. The simultaneous determination of Al, Mg, Mn, Ni, Ti and Zr is made possible by addition of 20 μl of 23M HF, which enables an efficient matrix removal at a pyrolysis temperature of 1200 °C. On the other hand, due to the higher volatility of Sb, an alternative approach, consisting of the removal of the organic matrix at 800 °C and the subsequent addition of 20 μl of 0.12 M HCl, was used for the determination of this element. In this way, antimony was efficiently vaporized at 1200 °C as a chloride, prior to the vaporization of Ag and Si. Quantitative results, obtained by using aqueous standards for calibration, were very satisfactory in terms of accuracy. The R.S.D. ranged between 8 and 12%. The results are hence promising, illustrating that the possibilities of ETV to deal with complex matrices are yet to be fully exploited. [Copyright &y& Elsevier]

Abstract: This work explores the performance of laser ablation—inductively coupled plasma mass spectrometry using different types of single-collector devices (sector field and time-of-flight instrumentation) for lead isotopic analysis of bronze coins, minted in the ancient city of Bilbilis. The aim of the study was achieving sufficient discrimination power to reveal similarities and differences for coins originating from different historical periods, and to obtain information on the possible source of the lead ores used in their production, while restricting the damage inflicted to the samples such that it is not visible to the naked eye. It was found that satisfactory results (RSD in the 0.15–0.30% range for 207Pb/206Pb and 208Pb/206Pb ratios) could be finally obtained, despite the noisy nature of signals generated upon ablation of the highly inhomogeneous coins, by means of a methodology based on: (a) selection of the line profiling ablation mode; (b) use of a dual pass spray chamber that permits the simultaneous introduction of a solution (containing thallium of known isotopic composition), thus resulting in a wet plasma that showed an increased robustness towards matrix effects and (c) detection using a TOF-ICPMS unit, which proved to be much better suited to deal with the transient signals obtained, while being also sufficiently sensitive to obtain good counting statistics, owing to the high lead level (average around 5%) present in the samples. Moreover, under these conditions, the simultaneous aspiration of the thallium spike permitted accurate correction for mass discrimination, such that it was not necessary to use external matrix-matched standards for calibration. [ABSTRACT FROM AUTHOR]

Abstract: This paper evaluates the potential of electrothermal vaporization–inductively coupled plasma mass spectrometry (ETV–ICPMS) for the direct determination of Hg in solid samples, using a 200Hg-enriched gaseous phase for calibration based on isotope dilution. Three different samples were studied, BCR CRM 320 River sediment, IAEA-086 Hair and a real (wet) freshwater fish sample (M1). The samples selected show important differences in their matrix composition, and especially the fish sample constitutes a challenge as a result of its high water content (≈80%). The main conclusion of the work is that the calibration approach investigated succesfully corrects for all the matrix effects (suppression) observed during Hg vaporization, allowing accurate values to be obtained in all cases. Moreover, practically the same operating conditions could be used for all sample types. The method finally proposed presents interesting features for the direct determination of this challenging element in solid samples, such as: a low sample consumption (a few milligrams), a high sample throughput (10 min/sample), a low limit of detection (6 ng g−1) and a reduced risk of analyte losses or contamination. Precision values depend on the homogeneity of the sample studied, and are typically in the vicinity of 10% RSD, except for the more inhomogenous river sediment (18% RSD). [Copyright &y& Elsevier]