Mass Balance Method for the SI Value Assignment of the Purity of Organic Compounds

Abstract

A mass balance method is described for determining the mass fraction of the main component of a high purity organic material. The resulting assigned value is established to be traceable to the SI and can be determined with a small associated measurement uncertainty. Pure organic materials with values and uncertainties determined in this way are necessary as primary calibrators of reference measurement systems in order to underpin the metrological traceability of routine measurement results. The method has been applied to materials in which the main components were respectively theophylline, digoxin, 17β-estradiol, and aldrin. Its performance has been validated in international comparisons coordinated by the BIPM and is in principle applicable to a wide structural range of stable, nonvolatile organic compounds. It has been successfully applied to mass fraction assignments when the main component is present in the range of (950-1000) mg/g and can achieve associated standard uncertainties ranging from 0.5 mg/g (for high purity materials or those containing well-characterized, stable minor components) to 2 mg/g (materials with a significant number or variety of impurities). It is in principle equally applicable to materials with a smaller mass fraction content of the main component.

The development of an efficient mass balance approach for the purity assignment of organic calibration standards

“…The mass fraction of volatile impurities (I VOL ), common organic solvents and/or water, can be evaluated by means of thermogravimetric analysis (TGA) at elevated temperatures, and Karl Fischer analysis provides a direct measure of water. Combustion or 'ashing' of the sample, at temperatures exceeding 600°C, completes the mass balance approach [9][10][11][12][13][14][15][16][17][18][19][20] with a measure of the non-volatile residue (I NVR ), usually assumed to be inorganic salts, in the sample. Summation of all volatile and non-volatile impurities and subtraction from 100 % completes the mass balance assessment of 'total purity' of a given material, which is calculated using Eq.…”

“…While this model no doubt holds true for many samples analysed by gas chromatography with flame ionisation detection (GC-FID), it is by no means failsafe and is particularly vulnerable when applied to samples analysed by highperformance liquid chromatography with UV detection (HPLC-UV) where subtle changes in structure can have a profound effect on the molar response. An alternative, metrologically robust approach, adopted in more recent times, is to identify each impurity and quantify via calibration [11,17,20], eliminating the potential for bias arising from the assumption described above. Unfortunately, this introduces the almost impossible task of securing calibration standards for each impurity, simultaneously increasing the time, and cost, associated with the certification process.…”

Metrological approaches to organic chemical purity: primary reference materials for vitamin D metabolites

“…Techniques which have supported this characterization include high performance liquid chromatography with UV absorbance-detection (HPLC-UV) and gas chromatography with flame ionization detection (GC-FID) for quantification of organic impurities, Karl Fischer titration for determination of water mass fraction, thermogravimetric analysis (TGA) for mass assessment of volatile constituents, and differential scanning calorimetry (DSC), when applicable, as a primary method for determination of molar purity. The combined estimate of relative impurities by these techniques (∑X % Impurity ) support a mass balance approach to purity determination (100 % −∑X % Impurity ) [3][4][5][6] that is commonly employed by producers of chemical standards and analytical laboratories. This method assumes that all impurities have been detected and quantified and that results of the individual techniques have been appropriately combined.…”

Developing a reference measurement procedure for free glycerol in human serum by two-step gas chromatography–isotope dilution mass spectrometry

“…In order to achieve metrological traceability, the purity of the glycerol calibration standard would need to be determined. As glycerol is highly hygroscopic, its purity cannot be determined by the commonly used mass balance approach [35]. We have therefore determined the concentration of the glycerol standard solution first, by using certified reference material (CRM) of tripalmitin in modified GC-IDMS experiments, which involves additional hydrolysis and derivatization steps.…”