Journal of The Korean Society of Inherited Metabolic disease (대한유전성대사질환학회지)

The Korea Society of Inherited Metabolic Disease (대한유전성대사질환학회)
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A Rapid, Simple Determination of Sulfur-containing Compounds and Methylmalonic Acid on Plasma using GC-MS-SIM for the Diagnosis of Homocysteinemia

혈장 중 황함유 화합물과 메틸말론산의 신속 간편한 분석법 개발; GC-MS-SIM을 이용한 호모시스테인혈증의 진단

  • Yoon, Hye-Ran (Department of Biomedical & Pharmaceutical Analyses, College of Pharmacy, Duksung Women's University) ;
  • Thapa, Maheshwor (Department of Biomedical & Pharmaceutical Analyses, College of Pharmacy, Duksung Women's University)
  • 윤혜란 (덕성여자대학교 약학대학 생 의약분석실) ;
  • 마헤샬타파 (덕성여자대학교 약학대학 생 의약분석실)
  • Published : 2015.12.25
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Abstract

Purpose: If early diagnosis is not made, patients with metabolic disorders as homocystinemia rapidly progress to physical defect or mental retardation resulted in storage of the toxic material into the brain. Therefore, it is necessary to develop an analytical method for a rapid screening and/or correct confirmation diagnosis. Methods: The standard solution of sulfur amino acids spiked plasma was subjected to protein precipitation with methanol, and then consecutively derivatized with trimethylsilyl (TMS) and trifluoroacyl (TFA) and determined by GC-MS. The formation of TMS derivative of the hydroxyl and TFA derivative of amino functional group was performed by BSTFA and MBTFA, respectively. Selective ion monitoring (SIM) mode was used for quantification with selected specific ions. Results: A calibration curve on standard spiked pooled plasma showed a linear relationship with correlation coefficient of 0.9936-0.9992 for all compounds over the range of 0.1-300 ng. The precision and accuracy were within S.D. of 1-15% and RSD of 1-15% for intra-day assay at 2 ng/mL, 15 ng/mL and 30 ng/mL. LOD and LOQ was 0.4 ng/mL and 4 ng/mL respectively. Conclusion: A rapid analytical method was developed to quantify sulfur amino acids and methyl malonic acid, after two-step derivatization procedure with good sensitivity and specificity on human plasma. Advantages of a new method are simplicity and rapidity. The method could be useful for routine analysis, diagnosis of homocysteinemia.

Keywords

References

  1. Wagner C, Decha-Umphai W, Corbin J. Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligand. J Biol Chem 1989;264:9638-42.
  2. Lee BC, Dikiy A, Kim HY, Gladyshev VN. Functions and evolution of selenoprotein methionine sulfoxidereductases. Biochim Biophys Acta 2009;1790:1471-7. https://doi.org/10.1016/j.bbagen.2009.04.014
  3. Savage DG, Lindenbaum J, Stabler SP, Allen RH. Sensitivity of serum methylmalonic acid and total homocysteine determinations for diagnosing cobalamin and folate deficiencies. Am J Med 1994;96:239-46. https://doi.org/10.1016/0002-9343(94)90149-X
  4. Nexo E, Hansen M, Rasmussen K, Lindgren A, Grasbeck R. How to diagnose cobalamin deficiency. Scand J Clin Lab Investig 1994;54(Suppl 219):61-76.
  5. Danesh J, Lewington S. Plasma homocysteine and coronary artery disease: systematic review of published epidemiological studies. J Cardiovasc Risk 1998;5: 229-32.
  6. Nygard O, Vollset SE, Refsum H, Brattstrom L, Ueland PM. Total homocysteine and cardiovascular disease. J Intern Med 1999;246:425-54. https://doi.org/10.1046/j.1365-2796.1999.00512.x
  7. Arson NA. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962;37:505-13. https://doi.org/10.1136/adc.37.195.505
  8. Gerritsen T, Vaughn JG, Waisman HA. The identification of homocysteine in the urine. Biochem Biophys Res Commun 1962;9:493-6. https://doi.org/10.1016/0006-291X(62)90114-6
  9. Stamler JS, Loscalzo J. Capillary zone electrophoretic detection of biological thiols and their S-nitrosated derivatives. Anal Chem 1992;64:779-85. https://doi.org/10.1021/ac00031a014
  10. Russell J., Rubenstein DL. Speciation and Quantitation of Underivatized and Ellman's Derivatized Biological Thiols and Disulfides by Capillary Electrophoresis. Anal Biochem 1996;242:136-44. https://doi.org/10.1006/abio.1996.0439
  11. Jaworska M, Szuli?ska G, Wilk M, Tautt J. Capillary electrophoretic separation of N-acetylcysteine and its impurities as a method for quality control of pharmaceuticals. J Chromatogr A 1999;853:479-85. https://doi.org/10.1016/S0021-9673(99)00727-X
  12. Bald E, Glowacki R, Drzewoski J. Determination by liquid chromatography of free and total cysteine in human urine in the form of its S-quinolinium derivative. J Chromatogr A 2001;913:319-29. https://doi.org/10.1016/S0021-9673(00)01202-4
  13. Katrusiak AE, Paterson PG, Kamencic H, Shoker A, Lyon AW. Pre-column derivatization high-performance liquid chromatographic method for determination of cysteine, cysteinyl-glycine, homocysteine and glutathione in plasma and cell extracts. J Chromatogr B 2001;758:207-12. https://doi.org/10.1016/S0378-4347(01)00182-7
  14. Melnyk S, Pogribna M, Pogribny I, Hine RJ, James SJ. A new HPLC method for the simultaneous determination of oxidized and reduced plasma aminothiols using coulometric electrochemical detection. J Nutr Biochem 1999;10:490-7. https://doi.org/10.1016/S0955-2863(99)00033-9
  15. Wayne A, Kleinman P, John P, Richie J. Status of Glutathione and Other Thiols and Disulfides in Human Plasma. Biochem Pharmacology 2000;60:19-29. https://doi.org/10.1016/S0006-2952(00)00293-8
  16. Hsi TS, Chuang MY. Preliminary Study on Reverse Pulse Amperometric detection in capillary electrophoresis for simultaneous determination of cysteine and cystine. J Chin Chem Soc 1998;45:827-30. https://doi.org/10.1002/jccs.199800125
  17. Briddon A. Total plasma homocysteine as part of the routine aminogram by ion-exchange chromatography Biochem Pharmacology 1998;15:235-9.
  18. De la Flor RR, RemySt, Montes-Bayon M. Sanz-Medel A. Determination of total homocysteine in human serum by capillary gas chromatography with sulfur-specific detection by double focusing ICP-MS. Anal Bioanal Chem 2003;377:299-305. https://doi.org/10.1007/s00216-003-2075-y
  19. Sigit JI, Hages M, Brensing KA, Frotscher U, Pietrzik K, Bergmann KV, et al. Total plasma homocysteine and related amino acids in end-stage renal disease patients measured by gas chromatography-mass spectrometry - comparison with the abbott IMx homocysteine assay and the HPLC method. Clin Chem Lab Med 2005;39:681-90.
  20. Svagera Z, Hanzlikova D, Simek P, Husek P. Study of disulfide reduction and alkyl chloroformatederivatization of plasma sulfur amino acids using gas chromatography-mass spectrometry. Anal Bioanal Chem 2012;402:2953-63. https://doi.org/10.1007/s00216-012-5727-y
  21. Windelberg A, Arseth O, Kvalheim G, Ueland PM. Automated assay for the determination of methylmalonic acid, total homocysteine, and related amino acids in human serum or plasma by means of methylchloroformate derivatization and gas chromatography-mass spectrometry. Clin Chem 2005;51:2103-9. https://doi.org/10.1373/clinchem.2005.053835
  22. Valerio A, Baldo G, Tessari P. A rapid method to determine plasma homocysteine concentration and enrichment by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom 2005;19:561-7. https://doi.org/10.1002/rcm.1808
  23. Mashima R, Nakanishi-Ueda T, Yamamotoa Y. Simultaneous determination of methionine sulfoxide and methionine in blood plasma using gas chromatographymass spectrometry. Anal Biochem 2003;313:28-33. https://doi.org/10.1016/S0003-2697(02)00537-7
  24. Johnson JM, Strobel FH, Reed M, Pohl J, Jones DP. A rapid LC-FTMS method for analysis of cysteine, cystine and cysteine/cystine steady-stateredox potential in human plasma. Clin Chim Acta 2008;396:43-8. https://doi.org/10.1016/j.cca.2008.06.020
  25. Weaving G, Rocks BF, Iversen SA. Simultaneous quantitation of homocysteine, cysteine, and methionine in plasma and urine by liquid chromatography-tandem mass spectrometry. Ann Clin Biochem 2006;43:474-80. https://doi.org/10.1258/000456306778904605
  26. Daniel RK. Introduction. In: Daniel RK, ed. Handbook of analytical derivatization reactions. New York: John Wiley and Sons, 1979;9-10.
  27. Food and drug administration http://www.fda.gov/downloads/Drugs/.../Guidances/ucm070107.pdf.