Coulometric method with titratable impurity analysis and mass balance method: convert acidimetric purity to chemical purity for SI-traceable highest standard of qNMR (potassium hydrogen phthalate), and verified by qNMR.

In this study, the coulometric method with titratable impurity analysis and the mass balance method were successfully applied in the quantification of the certified reference material of potassium hydrogen phthalate (KHP) with accurate metrological traceability of chemical purity value (99.983% with an expanded uncertainty of 0.024%, k = 2). In contrast to the general coulometric titration method, the coulometric method with titratable impurity analysis enables the conversion of acidimetric purity to chemical purity: The acidimetric purity was determined by coulometric titration method, and then the impurities that may be titrated as principal components were found as far as possible using various methods and the result of deducting these impurities from the acidimetric purity can be considered as chemical purity. The mass balance method also accounted for all possible types of impurities as much as possible to improve the accuracy of the determined result. The accuracy and reliability of the purity results were subsequently verified by a two-step quantitative nuclear magnetic resonance (qNMR) method. This KHP certified reference material was the first hydrophilic internal standard of qNMR (applied in polar solvents) with an expanded uncertainty lower than 0.03%, which will become a major reference standard in the organic chemistry traceable calibration chain, especially when evaluating hydrophilic organic compounds to obtain purity values with very low uncertainty.

Mass balance method for SI-traceable purity assignment of synthetic oxytocin.

Oxytocin is not only a significant peptide drug for enhancing uterine contractions, but also an emerging biomarker and therapeutic target of mental disorders in clinical practice. There is a pressing need for the standardization of oxytocin assays because of its low pharmaceutical quality and large variations among measurement approaches. International System of Units (SI)-traceable analytical methods and well-characterized pure reference materials are urgently needed to set up standard reference measurement systems in laboratory medicine, ensuring the accuracy and comparability of test results. Herein, the purity assignment of a synthetic oxytocin containing a disulfide linkage was established based on a mass balance method, which had never been performed for a cross-linked peptide. An in-house validated liquid chromatography-high-resolution tandem mass spectrometry method was developed for the determination of structurally-related impurities in the study material. Twenty-one structurally-related impurities including deamidations, oxidations, and amino acid insertions, etc. ranging from 0.05 mg g-1 to 15.65 mg g-1 were identified and quantified by applying a hierarchy calibration concept. This study subsequently discusses a fit for purpose assessment for non-peptide related impurities including water, non-volatile counterions, inorganic elements, and volatile organic compounds that were determined using coulometric Karl Fischer titration, ion chromatography, inductively coupled plasma mass spectrometry, and headspace gas chromatography-mass spectrometry, respectively. The resulting assigned value (796.5 mg g-1) is determined to be traceable to SI associated with a small measurement uncertainty of 6.5 mg g-1 (k = 2). The method developed in this study has been verified through an international key comparison jointly coordinated by the Bureau International des Poids et Mesures and the National Institute of Metrology.

Simultaneous removal of nitrate, copper and hexavalent chromium from water by aluminum-iron alloy particles.

Groundwater contamination is a worldwide concern and the development of new materials for groundwater remediation has been of great interest. This study investigated removal kinetics and mechanisms of nitrate, copper ion and hexavalent chromium (20-50 mg L-1) by particles of Al-Fe alloy consisting of 20% Fe in batch reactors from a single KNO3, CuSO4, Cu(NO3)2, K2Cr2O7 and their mixed solutions. The effects of contaminant interactions and initial pH of the solution were examined and the alloy particles before and after reaction were characterized by X-ray diffraction spectrometer, scanning electron microscopy and X-ray photoelectron spectroscopy. The removal mechanisms were attributed to chemical reduction [Cu(II) to Cu, NO3- to NH3 and Cr(VI) to Cr(III)] and co-precipitation of Cr(III)-Al(III)-Fe(III) hydroxides/oxyhydroxides. Cu(II) enhanced the rates of NO3- and Cr(VI) reduction and Cr(VI) was an inhibitor for Cu(II) and NO3- reduction. This study demonstrates that Al-Fe alloy is of potential for groundwater remediation.

Development of Dy, Ho, Er, Tm, and Sc mono-element standard solution certified reference materials (GBW08680-08684).

Dy, Ho, Er, Tm, and Sc mono-element solution certified reference materials (CRMs) with the certified value of 983.3 µg g-1 were developed with high-purity lanthanide oxides by using a novel purity characterization strategy. In the purity characterization process, complexometric titration was first employed to acquire the total metal ion concentration reacting with EDTA. Twenty-seven non-lanthanide impurities were measured by an external ICP-MS method with three multi-element calibration solution CRMs as calibrants. To avoid REO(H)+ interference from the main lanthanide matrix, two strategies namely LA-ICP-MS and MD-ICP-MS were optimized and used for the measurement of 15 rare earth impurities. The purity of lanthanide oxide material was obtained by subtracting the 42 impurities from the total metal ions reacting with EDTA. After purity characterization, the solution CRMs were prepared with a gravimetric method, and the CRM values were verified with corresponding NIST rare earth solution SRMs. It was shown that 15 units with duplicate analysis are enough to demonstrate the homogeneity of these candidate reference materials. The statistical results also showed no significant trends in stability tests for 24 months. The final uncertainties of the CRMs were evaluated by combining uncertainty contributions including the sample characterization and gravimetric preparation (uchar), between-bottle homogeneity (ubb), and stability (us). The relative expanded uncertainties of the five CRMs are 0.5%. These CRMs are primarily intended for use in the measurement and calibration procedures of lanthanide analysis in environmental and geological areas. Most importantly, the purity characterization strategy of this study will provide a new idea for the certification of high-purity and mono-element solution reference materials.

Development of certified reference materials for electrolytes in human serum (GBW09124-09126).

Three reference materials, at relatively low, middle, and high concentrations, were developed for analysis of the mass fractions of electrolytes (K, Ca, Na, Mg, Cl, and Li) in human serum. The reference materials were prepared by adding high purity chloride salts to normal human serum. The concentration range of the three levels is within ±20% of normal human serum. It was shown that 14 units with duplicate analysis is enough to demonstrate the homogeneity of these candidate reference materials. The statistical results also showed no significant trends in both short-term stability test for 1 week at 40 °C and long-term stability test for 14 months. The certification methods of the six elements include isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS), inductively coupled plasma optical emission spectroscopy (ICP-OES), atomic absorption spectroscopy (AAS), ion chromatography (IC), and ion-selective electrode (ISE). The certification methods were validated by international comparisons among a number of national metrology institutes (NMIs). The combined relative standard uncertainties of the property values were estimated by considering the uncertainties of the analytical methods, homogeneity, and stability. The range of the expanded uncertainties of all the elements is from 2.2% to 3.9%. The certified reference materials (CRMs) are primarily intended for use in the calibration and validation of procedures in clinical analysis for the determination of electrolytes in human serum or plasma. Graphical Abstract Certified reference materials for K, Ca, Mg, Na, Cl and Li in human serum (GBW09124-09126).