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Determination of purity values of amino acid reference materials by mass balance method: an approach to the quantification of related structure impurities

Abstract

A systematic procedure for the determination of purity values of amino acid reference materials was developed by use of mass balance method where four categories of impurities (related structure impurities (RSIs), water, organic solvent residue (OSR), and non-volatile residue (NVR)) were quantified separately. The amount of RSIs was determined using a combination of three quantification methods. To ensure metrological traceability in the determination of RSIs, at least one such impurity in each candidate amino acid reference material was quantified using liquid chromatography–isotope dilution tandem mass spectrometry (LC-IDMS/MS). Other RSIs were determined using external calibration liquid chromatography–tandem mass spectrometry (LC-MS/MS) or o-phthaldialdehyde (OPA) derivatization, followed by liquid chromatography–ultraviolet (LC-UV) measurement. As the UV absorption of most RSIs came basically from the same chromophore after OPA derivatization, a relative peak area approach was used in the LC-UV method to quantify the amount of RSIs by comparing their peak areas with that of a reference RSI. The reference RSI was pre-selected and the amount determined by LC-IDMS/MS separately. The absence of D-amino acids was confirmed using Marfey’s reagent derivatization, followed by LC-UV analysis. The amounts of water, OSR, and NVR were measured using Karl Fischer coulometry, gas chromatography–mass spectrometry (GC-MS) and thermogravimetry, respectively. By using this procedure, four amino acid (L-valine, L-leucine, L-isoleucine, and L-phenylalanine) certified reference materials (CRMs) were developed from the candidate materials. The homogeneity and stability of the CRMs were demonstrated by use of LC-IDMS/MS or OPA-LC-UV method, following the principles in ISO 17034 and ISO Guide 35.

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References

  1. Bantscheff M, Schirle M, Sweetman G, Rich J, Kuster B. Quantitative mass spectrometry in proteomics: a critical review. Anal Bioanal Chem. 2017;389:1017–31.

    Google Scholar 

  2. Brönstrup M. Absolute quantification strategies in proteomics based on mass spectrometry. Expert Rev Proteomics. 2004;1:503–12.

    PubMed  Google Scholar 

  3. Foutoulakis M, Lahm HW. Hydrolysis and amino acid composition analysis of proteins. J Chromatogr A. 1998;826:109–24.

    Google Scholar 

  4. Pritchard C, Groves KJ, Biesenbruch S, O’Connor G, Ashcroft AE, Arsene C, et al. Quantification of human growth hormone in serum with a labeled protein as an internal standard: essential considerations. Anal Chem. 2014;86:6525–32.

    PubMed  CAS  Google Scholar 

  5. Arsene CG, Ohlendorf R, Burkitt W, Pritchard C, Henrion A, O’Connor G, et al. Protein quantification by isotope dilution mass spectrometry of proteolytic fragments: cleavage rate and accuracy. Anal Chem. 2008;80:4154–60.

    PubMed  CAS  Google Scholar 

  6. Burkitt WI, Pritchard C, Arsene C, Henrion A, Bunk D, O’Connor G. Toward système international d’unité-traceable protein quantification: from amino acid to proteins. Anal Biochem. 2008;376:242–52.

    PubMed  CAS  Google Scholar 

  7. Kaiser P, Akerboom T, Ohlendorf R, Reinauer H. Liquid chromatography–isotope dilution–mass spectrometry as a new basis for the reference measurement procedure for hemoglobin A1c determination. Clin Chem. 2010;56:750–4.

    PubMed  CAS  Google Scholar 

  8. Bi J, Wu L, Yang B, Yang Y. Development of hemoglobin A1c certified reference material by liquid chromatography isotope dilution mass spectrometry. Anal Bioanal Chem. 2012;403:549–54.

    PubMed  CAS  Google Scholar 

  9. Wong L, Liu H, Yong Y, Liu Q, Lee TK. Improved reference measurement method for hemoglobin A1c by use of liquid chromatography–isotope dilution–tandem mass spectrometry. Clin Chem. 2015;61:435–6.

    PubMed  CAS  Google Scholar 

  10. Liu H, Wong L, Yong S, Liu Q, Lee TK. Achieving comparability with IFCC reference method for the measurement of hemoglobin A1c by use of an improved isotope-dilution mass spectrometry method. Anal Bioanal Chem. 2015;407:7579–87.

    PubMed  CAS  Google Scholar 

  11. Kato M, Kato H, Eyama S, Takatsu A. Application of amino acid analysis using hydrophilic interaction liquid chromatography coupled with isotope dilution mass spectrometry for peptide and protein quantification. J Chromatogr B. 2009;877:3059–64.

    CAS  Google Scholar 

  12. Kinumi T, Ichikawa R, Arimoto H, Takatsu A. Traceable amino acid analyses of proteins and peptides by isotope-dilution mass spectrometry using precolumn derivatization reagent. Anal Sci. 2010;26:1007–10.

    PubMed  CAS  Google Scholar 

  13. Jeong JS, Lim HM, Kim SK, Ku HK, Oh KH, Park SR. Quantification of human growth hormone by amino acid composition analysis using isotope dilution liquid-chromatography tandem mass spectrometry. J Chromatogr A. 2011;1218:6596–602.

    PubMed  CAS  Google Scholar 

  14. Wu L, Yang B, Bi J, Wang J. Development of bovine serum albumin certified reference material. Anal Bioanal Chem. 2011;400:3443–9.

    PubMed  CAS  Google Scholar 

  15. Yim JH, Yoon I, Yang HJ, Kim SK, Park SR, Lee YM, et al. Quantification of recombinant human erythropoietin by amino acid analysis using isotope dilution liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem. 2014;406:4401–9.

    PubMed  CAS  Google Scholar 

  16. Muñoz A, Kral R, Schimmel H. Quantification of protein calibrants by amino acid analysis using isotope dilution mass spectrometry. Anal Biochem. 2011;408:124–31.

    PubMed  Google Scholar 

  17. Lowenthal MS, Yen J, Bunk DM, Phinney KW. Certification of NIST standard reference material 2389a, amino acids in 0.1 mol/L HCl – quantification by ID LC-MS/MS. Anal Bioanal Chem. 2010;397:511–9.

    PubMed  CAS  Google Scholar 

  18. Kato M, Yamazaki T, Kato H, Eyama S, Goto M, Yoshioka M, et al. Development of high-purity certified reference materials for 17 proteinogenic amino acids by traceable titration methods. Anal Sci. 2015;31:805–14.

    PubMed  CAS  Google Scholar 

  19. Josephs RD, Martos G, Li M, Wu L, Melanson JE, Quaglia M, et al. Establishment of measurement traceability for peptide and protein quantification through rigorous purity assessment – a review. Metrologia. 2019;56(4):044006.

    CAS  Google Scholar 

  20. Westwood S, Choteau T, Daireaux A, Josephs RD, Wielgosz RI. Mass balance method for the SI value assignment of the purity of organic compounds. Anal Chem. 2013;85:3118–26.

    PubMed  CAS  Google Scholar 

  21. Quan C. Establishment of the purity values of carbohydrate certified reference materials using quantitative nuclear magnetic resonance and mass balance approach. Food Chem. 2014;153:378–86.

    PubMed  CAS  Google Scholar 

  22. Nogueira R, Garrido BC, Borges RM, Silva GEB, Queiroz SM, Cunha VS. Development of a new sodium diclofenac certified reference material using the mass balance approach and 1H qNMR to determine the certified property value. Eur J Pharm Sci. 2013;48:502–13.

    PubMed  CAS  Google Scholar 

  23. Ishikawa K, Hanari N, Shimizu Y, Ihara T, Nomura A, Numata M, et al. Mass balance method for purity assay of phthalic acid esters: development of primary reference materials as traceability sources in the Japan Calibration Service Systerm. Accred Qual Assur. 2011;16:311–22.

    CAS  Google Scholar 

  24. Ma K, Wang H, Zhao M, Xing J. Purity determination and uncertainty evaluation of theophylline by mass balance method, high performance liquid chromatography and differential scanning calorimetry. Anal Chim Acta. 2009;650:227–33.

    PubMed  CAS  Google Scholar 

  25. Gong H, Huang T, Yang Y, Wang H. Purity determination and uncertainty evaluation of folic acid by mass balance method. Talanta. 2012;101:96–103.

    PubMed  CAS  Google Scholar 

  26. Westwood S, Josephs RD, Daireaux A, Wielgosz RI, Davies SR, Wang H, et al. Final report on key comparison CCQM-K55.a (estradiol): an international comparison of mass fraction purity assignment of estradiol. Metrologia. 2012;49:08009.

    Google Scholar 

  27. Westwood S, Josephs RD, Choteau T, Daireaus A, Mesquida C, Wielgosz R, et al. Final report on key comparison CCQM-K55.b (aldrin): an international comparison of mass fraction purity assignment of aldrin. Metrologia. 2012;49:08014.

    Google Scholar 

  28. Westwood S, Josephs RD, Choteau T, Daireaux A, Wielgosz R, Davies SR, et al. Final report on key comparison CCQM-K55.c (L-(+)-valine): characterization of organic substances for chemical purity. Metrologia. 2014;51:08010.

    Google Scholar 

  29. Westwood S, Josephs RD, Choteau T, Daireaux A, Stoppacher N, Wielgosz R, et al. Mass fraction assignment of folic acid in a high purity material. Metrologia. 2018;55:08013.

    Google Scholar 

  30. Carlos G, Comiran E, de Oliveira MH, Limberger RP, Bergold AM, Fröehlich PE. Development, validation and comparison of two stability-indicating RP-LC methods using charged aerosol and UV detectors for analysis of lisdexamfetamine dimesylate in capsules. Arab J Chem. 2016;9:S1905–14.

    CAS  Google Scholar 

  31. Gaber Y, Åkerman CO, Hatti-Kaul R. Environmentally evaluated HPLC-ELSD method to monitor enzymatic synthesis of a non-ionic surfactant. Chem Cent J. 2014;8:33.

    PubMed  PubMed Central  Google Scholar 

  32. Mellon EF, Hoover SR. Hygroscopicity of amino acids and its relationship to the vapor phase water absorption of proteins. J Am Chem Soc. 1951;73:3879–82.

    CAS  Google Scholar 

  33. Chen Y, Liu Q, Yong S, Lee TK. High accuracy analysis of glucose in human serum by isotope dilution liquid chromatography-tandem mass spectrometry. Clin Chim Acta. 2012;413:808–13.

    PubMed  CAS  Google Scholar 

  34. Teo HL, Wong L, Liu Q, Teo TL, Lee TK. Simple and accurate measurement of carbamazepine in surface water by use of porous membrane-protected micro-solid-phase extraction coupled with isotope dilution mass spectrometry. Anal Chim Acta. 2016;912:49–57.

    PubMed  CAS  Google Scholar 

  35. Henderson JW, Richer RD, Bidlingmeyer BA, Woodward C. Rapid, accurate, sensitive, and reproducible HPLC analysis of amino acids. http://www.agilent.com/cs/library/chromatograms/59801193.pdf. Accessed 20 May 2020

  36. Novatchev N, Holzgrabe U. Evaluation of the impurity profile of amino acids by means of CE. J Pharm Biomed Anal. 2001;26:779–89.

    PubMed  CAS  Google Scholar 

  37. Kopec S, Holzgrabe U. Amino acids: aspects of impurity profiling by means of CE. Electrophoresis. 2007;28:2153–67.

    PubMed  CAS  Google Scholar 

  38. Kato M, Yamazaki T, Goto M, Yoshioka M, Kato H, Takatsu A. Comparison of three amino acid analysis methods and their application to the amino acid impurity analysis for the development of high-purity amino acid certified reference materials. Accred Qual Assur. 2014;18:481–9.

    Google Scholar 

  39. Huang T, Zhang W, Dai X, Zhang X, Quan C, Li H, et al. Precise measurement for the purity of amino acid and peptide using quantitative nuclear magnetic resonance. Talanta. 2014;125:94–101.

    PubMed  CAS  Google Scholar 

  40. Szókán G, Mezö G, Hudecz F. Application of Marfey’s reagent in racemization studies of amino acids and peptides. J Chromatogr. 1988;444:115–22.

    PubMed  Google Scholar 

  41. Bhushan R, Brückner H. Marfey’s reagent for chiral amino acid analysis: a review. Amino Acids. 2004;27:231–47.

    PubMed  CAS  Google Scholar 

  42. Lee YC. Method validation for HPLC analysis of related substances in pharmaceutical drug products. In: Chan CC, Lam H, Lee YC, Zhang XM, editors. Analytical method validation and instrument performance verification. Hoboken: Wiley; 2004. p. 27–49.

    Google Scholar 

  43. Dunn MS, Brophy TW. Decomposition points of the amino acids. J Biol Chem. 1932;99:221–9.

    CAS  Google Scholar 

  44. Wesolowski M, Erecinska J. Relation between chemical structure of amino acids and their thermal decomposition. J Therm Anal Calorim. 2005;82:307–13.

    CAS  Google Scholar 

  45. ISO Guide 35:2017 Reference materials – guidance for characterisation and assessment for homogeneity and stability

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Acknowledgements

The authors are grateful to the Health Sciences Authority, Singapore, for the support of this project. The authors would also like to thank Dr. Lingkai Wong for valuable discussion.

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Correspondence to Qinde Liu.

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Liu, H., Cheow, P.S., Yong, S. et al. Determination of purity values of amino acid reference materials by mass balance method: an approach to the quantification of related structure impurities. Anal Bioanal Chem 412, 8023–8037 (2020). https://doi.org/10.1007/s00216-020-02936-7

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