HPLC direct purity assay using ultra-purified materials as primary standards

Reference materials certified for purity are essential to ensure harmonization of analytical measurements. LGC is currently certifying these materials using an indirect multi-method approach quantifying impurities: Related substances using high-performance liquid chromatography, gas chromatography (GC), differential scanning calorimetry; Residual solvents using headspace GC coupled to mass spectrometry; Inorganic content using ashing, acid digest ion couple plasma mass spectrometry or thermogravimetric analysis; Water using oven coulometric Karl Fischer/direct addition coulometric Karl Fischer. Related substances are not straightforward to quantify without an appropriate standard due to possible difference in response factor for the impurity relative to the main compound. In this article, existing LGC RMs certified for purity were purified further using semi-preparative HPLC. These ultra-purified organic substances were virtually free of related substances making their purity assessment faster and more straightforward, i.e., no need to identify impurities and subsequently quantify them. After characterization, these ultra-purified standards were used as calibrants to determine directly the mass fraction of the analyte in the original CRM using exact matching single-point HPLC calibration. This new approach opens the possibility of certifying the purity of low purity substances with a relative small uncertainty without the need of identifying the impurities present in the sample.     

低温热分析标准物质的研制

研制了两种0~100℃热分析标准物质,分别为金属镓和水杨酸苯酯标准物质。研制的标准物质具有良好的均匀性和稳定性,采用与NIST,LGC相应标准物质比较的方法定值。NIST为SRM 2234镓,其定值采用288.6~314.35 K范围内的绝热热量计测得温度及热量值;LGC用绝热法为水杨酸苯酯的熔化温度和熔化热定值,两种方法都可以直接溯源至SI单位。对定值结果的不确定度进行了分析和评定。镓和水杨酸苯酯标准物质的熔化温度分别为(29.77±0.20)℃(k=2),(41.81±0.34)℃(k=2);熔化热分别为(80.52±0.48)J/g(k=2),(88.94±0.62)J/g(k=2)。研制的两种标准物质满足国家标准物质的技术要求,申报已获批准。     

LGC五种熔点标准物质的定值

介绍英国政府化学家研究所（LGC）研制的五种熔点标准物质的熔点和凝固点的定值方法、定值结果及不确定度的估计。     

加替沙星纯度标准物质研制

研制加替沙星纯度标准物质。采用质量平衡法和氢谱定量核磁法对加替沙星纯度标准物质候选物进行纯度定值,采用卡尔费休法和热重分析法准确测量了影响主成分纯度的水分含量,并考察了水分含量的稳定性。开展了加替沙星纯度定值、均匀性检验、稳定性考察以及不确定度评估。结果表明,加替沙星纯度标准物质的纯度值为93.1%,扩展不确定度为0.6%(k=2),水分含量为6.6%,特性量值均匀性良好,6个月稳定性可靠,被认定为国家二级标准物质,编号为GBW(E) 100476。研制的加替沙星纯度标准物质填补了国内空白,同时也为吸湿性较强的药物纯度标准物质研制过程中水分测定提供了参考与借鉴。     

Purity assessment for avoparcin

Well-characterized pure-substance reference materials for the use as calibrants are essential to establish the metrological traceability of the results of chemical measurements. Normally, the characterization of this type of reference material is conducted through a thorough purity assessment of the compound concerned. For this reason, studies on purity assessment, especially for neat organic compounds, continues as an important part of work being undertaken by metrological institutions around the world. Among others, the need for certified pure reference standards continues to increase for residues analysis in foods, particularly for those compounds which have been banned for food safety reasons, but their residues in foods are still monitored under food surveillance program in many countries. In this respect, avoparcin serves as a very good example where testing laboratories have difficulties in obtaining traceable and comparable results on determination of avoparcin in food matrix samples due, in part, to the unavailability of certified pure-substance reference material as calibrant. In this study, it was attempted to assess the purity of a commercially available test material of avoparcin using the mass balance approach. The objective of this paper is to share the difficulties encountered during the course of purity assessment and how they were addressed. As expected, the most challenging part of work was to identify and estimate the amount of unknown impurities, both organic and inorganic-related ones, given the chemical structure and properties of avoparcin. For instance, avoparcin exists in two forms in the test material, i.e., α- and β-avoparcin, and they were found to be susceptible to hydrolysis under certain conditions.     

Differential scanning calorimetry to measure the purity of polycyclic aromatic hydrocarbons

The application of differential scanning calorimetry (DSC) for purity determination is well documented in literature and is used amongst others in the analysis of pure organic crystalline compounds. The aim of this work is to examine whether the DSC method for purity determination consistently produces values for the purity of polycyclic aromatic hydrocarbons (PAHs) which are sufficiently accurate as required for the certification of reference materials. For this purpose, 34 different existing PAH certified reference materials were tested. The DSC results are shown to be consistent with the results obtained by other methods assessing the organic impurities content in PAHs, like gas chromatography (GC), high performance liquid chromatography (HPLC) and mass spectrometry. Significant differences between the measured values and the certified purity values were observed only in a limited number of cases.     

Determination of the purity of acidimetric standards by constant-current coulometry, and the intercomparison between CRMs

The accuracy and uncertainty of the coulometric measurement results of reference materials for acidimetric titration were examined in this study. The results for amidosulfuric acid and potassium hydrogen phthalate are presented. The uncertainty was investigated by examining the dependency on the sample size and on the electrolysis current. Changes in the titration parameters did not result in any significant effects on the titration results. Acidimetric standards with the certified value linked to the SI were developed. In addition, the intercomparison of acidimetric standards was carried out by gravimetric titration, and the relationship between our coulometric results was determined. Furthermore, due to recent internationalization, not only the traceability to the SI but also the relationship and consistency of their analytical data have gained increasing importance. Our results were validated using certified reference materials (CRMs) obtained from different National Metrology Institutes (NMIs), and their relationships are presented. Presented at -- “BERM-10” -- April 2006, Charleston, SC, USA.     

Evaluation of certified reference materials for oxidation-reduction titration by precise coulometric titration and volumetric analysis

The accuracy and uncertainty of coulometric titration of Japanese certified reference materials (CRMs) for oxidation-reduction titration were examined in this study. The results for potassium dichromate, sodium oxalate, and potassium iodate are presented. Potassium dichromate was directly determined by coulometric titration, and sodium oxalate and potassium iodate were determined by volumetric analysis using potassium dichromate assigned by coulometry.The uncertainty of the method was investigated by examining the dependency on the sample size and on the electrolysis current. Changes in the titration parameters did not result in any significant effects on the titration results. The coulometric system used primarily consists of a constant current source, timer, switching circuit, indicator unit, and voltmeter. They were controlled using the coulometry software by a PC/AT compatible computer. A highly automated coulometric system achieves repeatabilities of less than one part in 30,000 (k = 2) and uncertainties of less than one part in 15,000 (k = 2). In addition, using volumetric method, SI units traceable sodium oxalate and potassium iodate (purity standards for redox reaction) CRMs were developed.Reference materials for volumetric analysis are the most basic substances used in analytical chemistry. These materials are analyzed by several analytical methods and are produced globally; however, their purities have not been compared at the international level. Therefore, the relationship between the purity and reliability of these materials has not yet been established. In this paper, we determine the relationship between these parameters by titrating each material obtained from different laboratories.     

Strategies implemented at LNE to establish the traceability of environmental measurements

LNE is actively involved in the development of reference procedures in the domains of organic and inorganic chemistry and in gas analysis. Moreover, production of certified reference materials (CRMs), certification of calibration standards, and providing reference values for proficiency testing schemes (PTS) are fields well settled to ensure the traceability of measurements in environmental monitoring. The paper presents some representative examples of these activities recently realised in our laboratory. Presented at BERM-11, October 2007, Tsukuba, Japan.     

Determination of boron in ceramic reference materials by prompt gamma activation analysis using focused neutron guided beam of JRR-3M

Prompt gamma activation analysis using a focused thermal neutron guided beam at JAEA JRR-3M was applied to the determination of B in ceramic certified reference materials (BAM CRM S-003 Silicon Carbide Powder and NMIJ CRM 8004-a Silicon Nitride Powder). Cl and Si were used as internal standards to obtain linear calibration curves of B. The analytical result of B in BAM CRM S-003 was in good agreement with the certified value. The relative expanded measurement uncertainties (k = 2) were 4.8% for BAM CRM S-003 and 4.9% for NMIJ CRM 8004-a.     

Evaluation of measurement uncertainties for the determination of total metal content in soils by atomic absorption spectrometry

In this work estimation of measurement uncertainties associated with the total metal content in soils was done by an intralaboratory approach based on method validation and quality control data, and using two certified reference materials (CRM). CRM and soil samples were analyzed following procedures based on the methods that are applied to silicate materials. All elements were determined by atomic absorption spectrometry following a quality assurance program previously established. Quality control actions were implemented in order to provide reliable data. The precision under within-laboratory reproducibility conditions was estimated from triplicate analysis. The trueness component was determined as recovery of the analyte from CRMs: soil sample, SO-2 and river clay sediment, LGC 6139. Combined measurement uncertainty was expressed in terms of precision and recovery uncertainties and the later further split on CRM replicate analysis and uncertainty of the certified value components. The results obtained are critically discussed on the basis of the different contributions. For the selection of the reference material, the CRM dependent terms are critically compared in order to fulfill specific requirements. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Determination of perfluorinated compounds in aquatic organisms: a review

Bioaccumulation of PFAS in aquatic organisms is an environmental problem of growing concern around the world. This problem has been tackled by regulatory bodies by proposing EQS for biota in EU water bodies and tolerable daily intake for food. The introduction of regulatory limits requires the availability of harmonised and validated analytical methods of sufficient sensitivity. This paper reviews recent advances in analytical methods for analysis of PFAS in aquatic organisms. The methods available for biota analysis are mostly based on three extraction procedures: ion-pair extraction, solvent liquid extraction, and alkaline digestion. The resulting extracts are then subjected to different clean-up or enrichment steps on solid adsorbents, for example graphitized carbon black, C₁₈, and WAX phases. All methods reviewed in this work give reliable results but are partially validated only, because of the lack of certified reference materials and regular interlaboratory exercises. The few interlaboratory exercises performed on real unspiked samples did not afford satisfactory results for PFAS other than PFOS, especially for matrices with high lipid content, for example mussels. The reasons for those partially negative results have been identified, and can mainly be attributed to calibration procedures and availability and purity of standards. The urgent need for certified reference materials for this type of analysis is emphasized.     

Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry

Purity determination of pure organic substance is essential for the establishment of traceability to SI units. A mass balance method was employed to determine the purity of theophylline certified reference materials (CRM), compared with high performance liquid chromatography (HPLC) and differential scanning calorimetry (DSC). In the approach of the mass balance, the impurities were identified by ion trap time-of-flight mass spectrometer (IT-TOF-MS) and quantified by HPLC. The purity of theophylline CRM determined by mass balance method was 99.82% with an extended uncertainty of 0.1% (k = 2). The uncertainty evaluation of purity demonstrated that the accuracy of the mass balance method is better than that of HPLC and DSC. It indicated that the mass balance is suitable for the CRM and pharmaceutical standards.     

Establishing a basis for nuclear archaeometry in Australia using the 20 MW OPAL research reactor

The k ₀-method of standardisation for instrumental neutron activation analysis (INAA) has been used at the OPAL research reactor to determine the elemental composition of three certified reference materials: coal fly ash (SRM 1633b), brick clay (SRM 679) and Montana soil (SRM 2711). Of the 41 certified elements in the three materials, 88 percent were within five percent of the certified values and all determinations were within 15 percent of the certified values. The average difference between the measured and certified values was 0.1 percent, with a standard deviation of 4.1 percent. Since these reference materials are widely used as standards in the analysis of archaeological ceramics by INAA, it has been concluded that the INAA facility in Australia is particularly well-suited for nuclear archaeometry.     

基准试剂纯度定值研究

本文介绍了基准试剂纯度定值装置的工作原理,研究制作了用于反映库仑滴定终点的终点指示器,并对基准试剂的纯度分析方法进行了研究,使定值精度达到了国内外先进水平。     

Microwave digestion of sediment, soils and urban particulate matter for trace metal analysis

A microwave digestion technique was developed to determine the content of nine heavy metals in sediments and soils. The digests were subsequently analysed by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The metals determined were Ca, Mg, Fe, Mn, Zn, Cr, Cd, Cu, Pb and V. The digestion was achieved by using an acid mixture of HNO₃, HF and distilled H₂O. The experimental study was conducted using four standard reference materials (SRMs): sewage sludge (LGC6136), marine sediment (PACS-1), urban particulate matter (NIST 1648) and coal carbonisation site soil (LGC6138). Two different programs were examined to determine which was optimal for the digestion of real environmental samples. The accuracy and precision of the two digestion programs for the analysis of the SRMs were compared. From the results obtained, the microwave program providing a maximum of power of 650 W and a cycle time of 51 min resulted in the best analytical performance. The experimental results obtained were in good agreement with the certified values and demonstrated that the proposed method is precise and accurate.     

Primary standards in activation analysis

The availability of natural matrix reference materials evaluated for trace element content has resulted in their widespread use as standards (i.e., calibration materials; comparators) for instrumental neutron activation analysis (INAA). Due to the uncertainties associated with their certified values, the limited number available, and the relative matrix independence of INAA, these reference materials are more properly utilized as quality assessment materials, after calibration of the INAA analytical system with true primary standards. Terminology is defined, the use of matrix reference materials to evaluate the analytical system is discussed, techniques for the accurate preparation of primary standards for trace element analyses are reviewed, and necessary precautions in the accurate comparison of samples to standards are presented.     

Are analytical standards and reagents really reliable?

Quality assurance is one of the major challenges in analytical chemistry, whatever the scope of application. The quality of analytical standards is very seldom questioned; however, sometimes odd results are obtained, and all the other potential sources of discrepancies are eliminated. So, we investigated the reliability of three analytical standards and reagents implemented for radiochemical and chemical characterizations of nuclear waste. In particular, this work examined the purity of a source of tritiated dodecane, the trueness of a certified concentration value and the purity for a diethylenetriaminepentaacetic acid (DTPA) reagent and the trueness of a certified concentration value for a multi-anion standard used in an interlaboratory comparison exercise. It was shown that the source of tritiated dodecane contains 60 % of tritiated impurities. The trueness of the DTPA concentration certified by the supplier was questioned due to the presence of impurities in the solution. It was proven that the long-term stability of the multi-anion standard was not guaranteed for nitrite. The results clearly demonstrated that, despite the certificates delivered by the suppliers, caution has to be taken toward the reliability of the analytical standards and reagents.     

Development of certified reference materials of high-purity volatile organic compounds: purity assay by the freezing-point depression method

For accurate measurement of concentrations of substances by instrumental analysis, reliable calibration standards are needed. In Japan, national reference materials are supplied under the national standards dissemination system named the Japan Calibration Service System (JCSS). In JCSS, calibration standards for the analysis of environmental pollutants are supplied. For the traceability to the SI of reference materials for calibration in JCSS, the National Metrology Institute of Japan (NMIJ) is developing high-purity reference materials of volatile organic compounds (VOCs) as NMIJ CRMs. The freezing-point depression method, which has potential as a primary method of measurement, is employed for the determination of property value. In this paper, a development scheme of certified reference materials of high-purity VOCs is described. Presented at BERM-11, October 2007, Tsukuba, Japan.     

A comparison of synthetic irradiation-resistant multielement standards for activation analysis

An aluminium matrix and a phenolformaldehyde polymer were tested as base materials for multielement standards resistant to high neutron doses in activation analysis. Interlaboratory analyses showed that these standards can be certified for the concentrations of the majority of introduced elements.