An international comparison of mass fraction purity assignment of theophylline: CCQM Pilot Study CCQM-P20.e (Theophylline)

Westwood, Steven; Josephs, R D; Daireaux, Adeline; Wielgosz, Robert; Davies, Stephen; Kang, Mingchao; Ting, Huang; Phillip, R; Malz, Frank; Shimizu, Yoshiaki; Frías, Evangelina Camacho; Pérez, Manuel Enrique Belloso; Apps, P.J.; Fernandes-Whaley, Maria; Vos, Betty-Jayne De; Wiangnon, Kanjana; Ruangrittinon, Nidapan; Wood, Sylvia H.; Duewer, David L.; Schantz, Michele M.; Bedner, Mary; Hancock, Diane K.; Esker, J

doi:10.1088/0026-1394/46/1a/08019

Cited by 7 publications

(14 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This can be determined either by approaches that measure the mass fraction or mole fraction of the main component directly, or by indirect approaches that identify and estimate the mass fraction of the individual impurities and/or distinct classes of impurities present in the material and, by subtraction, provide a measure for the main component of the material [5]. These approaches have been successfully applied to a large variety of small molecules [6][7][8][9][10]. The quantification of larger molecules is complicated by the fact that they can exhibit higher order structures, and that characterization of the primary structure of the molecule maybe 5 / 28 insufficient to correlate the amount of the molecule to its biological activity.…”

Section: Rationale/purposementioning

confidence: 99%

Pilot study on peptide purity—synthetic human C-peptide

Josephs

Song

et al. 2017

Metrologia

Self Cite

View full text Add to dashboard Cite

Under the auspices of the Protein Analysis Working Group (PAWG) of the Comité Consultatif pour la Quantité de Matière (CCQM) a pilot study, CCQM-P55.2, was coordinated by the Bureau International des Poids et Mesures (BIPM) and the Chinese National Institute of Metrology (NIM). Four Metrology Institutes or Designated Institutes and the BIPM participated. Participants were required to assign the mass fraction of human C-peptide (hCP) present as the main component in the comparison sample for CCQM-P55.2. The comparison samples were prepared from synthetic human hCP purchased from a commercial supplier and used as provided without further treatment or purification. hCP was selected to be representative of the performance of a laboratory's measurement capability for the purity assignment of short (up to 5 kDa), non-cross-linked synthetic peptides/proteins. It was anticipated to provide an analytical measurement challenge representative for the value-assignment of compounds of broadly similar structural characteristics. The majority of participants used a quantitative nuclear magnetic resonance spectroscopy (qNMR) corrected for peptide impurities. Other participants provided results obtained by peptide impurity corrected amino acid analysis (PICAA) or elemental analysis (PICCHN). It was decided to assign reference values based on the KCRVs of CCQM-K115 for both the hCP mass fraction and the mass fraction of the peptide related impurities as indispensable contributor regardless of the use of PICAA, mass balance or any other approach to determine the hCP purity. This allowed participants to demonstrate the efficacy of their implementation of the approaches used to determine the hCP mass fraction. In particular it allows participants to demonstrate the efficacy of their implementation of peptide related impurity identification and quantification. The assessment of the mass fraction of peptide impurities is based on the assumption that only the most exhaustive and elaborate set of results is taken for the calculation of the reference value. The reference value for the peptide related impurity mass fractions of the material was 83.3 mg/g with a combined standard uncertainty of 1.5 mg/g. Inspection of the degree of equivalence plots for the mass fraction of peptide impurities and additional information obtained from the peptide related impurity profile indicates that in many cases only a very small number of impurities have been identified and quantified resulting in an underestimation of the peptide related impurity mass fractions. The reference value for the mass fraction of hCP for CCQM-KP55.2 is 801.8 mg/g with a corresponding combined standard uncertainty of 3.1 mg/g. Inspection of the degree of equivalence plots for CCQM-P55.2 for the mass fraction of hCP shows that three results agree with the reference value. Main text To reach the main text of this paper, click on Final Report. The final report has been peer-reviewed and approved for publication by the CCQM.

show abstract

Section: Rationale/purposementioning

confidence: 99%

Pilot study on peptide purity—synthetic human C-peptide

Josephs

Song

et al. 2017

Metrologia

Self Cite

View full text Add to dashboard Cite

show abstract

“…The preferred practice of using integrals of sufficient width to include the corresponding 13 C satellites was only possible with 2 (186 Hz integral width), integral widths of peaks representing 3 (89 Hz) and 4 (23 Hz) being significantly reduced to avoid interference with neighbouring peaks. Even so, the integral representing 3 at 7.88 ppm included a signal for 4 and the downfield 13 .HCl Fig. 1 The structures of key compounds discussed in the text evaluated and subtracted from the integral value.…”

Section: Gas Chromatography With Flame Ionisation Detectionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

View full text Add to dashboard Cite

The purity determination of organic calibration standards using the traditional mass balance approach is described. Demonstrated examples highlight the potential for bias in each measurement and the need to implement an approach that provides a cross-check for each result, affording fit for purpose purity values in a timely and cost-effective manner. Chromatographic techniques such as gas chromatography with flame ionisation detection (GC-FID) and high-performance liquid chromatography with UV detection (HPLC-UV), combined with mass and NMR spectroscopy, provide a detailed impurity profile allowing an efficient conversion of chromatographic peak areas into relative mass fractions, generally avoiding the need to calibrate each impurity present. For samples analysed by GC-FID, a conservative measurement uncertainty budget is described, including a component to cover potential variations in the response of each unidentified impurity. An alternative approach is also detailed in which extensive purification eliminates the detector response factor issue, facilitating the certification of a super-pure calibration standard which can be used to quantify the main component in less-pure candidate materials. This latter approach is particularly useful when applying HPLC analysis with UV detection. Key to the success of this approach is the application of both qualitative and quantitative (1)H NMR spectroscopy.

show abstract

“…A purity assignment was carried out on a spiked theophylline (1, Figure 1) containing gravimetrically assigned amounts of caffeine and theobromine. 6 Two independent LC methods, using different columns, solvent systems, and detectors (respectively UV absorption at 273 nm and MS/MS with positive ESI) were validated using the common xanthines theophylline, theobromine, caffeine, 3-methylxanthine, and 7-methylxanthine as model compounds. Application of both methods to the sample, with quantification by external calibration for each identified minor component, and quantification from the relative area response for one unidentified impurity, produced after combination of the data a related structure impurity profile for the material as provided in Table 1 of the Supporting Information.…”

Section: Fraction Puritymentioning

confidence: 99%

“…• Theophylline (1) (high purity and spiked with caffeine and theobromine) 6 • Digoxin (2) 7 • Estradiol (3) 8 • Aldrin (4) 9 In the discussions below, the reference values used to validate the performance of the BIPM approach for mass fraction assignment refer to the best estimates for the content of the main component and its associated impurity profile in each comparison material. These reference values were derived from and agreed to by peer review of the combined participant data.…”

mentioning

confidence: 99%

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

et al. 2013

View full text Add to dashboard Cite

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.

show abstract

An international comparison of mass fraction purity assignment of theophylline: CCQM Pilot Study CCQM-P20.e (Theophylline)

Cited by 7 publications

References 0 publications

Pilot study on peptide purity—synthetic human C-peptide

Pilot study on peptide purity—synthetic human C-peptide

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

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

Contact Info

Product

Resources

About