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Simultaneous determination of 18 d-amino acids in rat plasma by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method: application to explore the potential relationship between Alzheimer’s disease and d-amino acid level alterations

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Abstract

d-Amino acids are increasingly being recognized as important signaling molecules, and abnormal levels of d-amino acids have been implicated in the pathogenesis of Alzheimer’s disease. To evaluate the potential relationship between Alzheimer’s disease and d-amino acids, a simple, sensitive, and reliable UPLC-MS/MS method with pre-column derivatization was developed and validated for simultaneous determination of 18 d-amino acids in rat plasma. The analytes were extracted from plasma samples by a protein precipitation procedure, and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]. Chromatographic separation was achieved using an ACQUITY UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with a mobile phase composed of acetonitrile containing 8 mM ammonium hydrogen carbonate at a flow rate of 0.6 mL min−1. The analytes were detected by electrospray ionization in positive ion multiple reaction monitoring modes. Under the optimum experimental conditions, all the linear regressions were acquired with r > 0.9932. The limits of quantitation of all derivatized d-amino acids were within 0.05–40.0 ng mL−1 in rat plasma. The intra- and inter-day precisions, expressed as percentage relative standard deviations (%RSD), were within the range of 12.3 and 10.1 %, respectively. The recoveries for all the analytes were observed over the range of 82.8–100.5 % with RSD values less than 12.5 %. Finally, the proposed method was successfully applied to simultaneous determination of the 18 d-amino acids in plasma from Alzheimer’s disease rats and age-matched normal controls. Results showed that the concentrations of d-serine, d-aspartate, d-alanine, d-leucine, and d-proline in Alzheimer’s disease rat plasma were significantly decreased compared with those in normal controls, while d-phenylalanine levels increased. It was revealed that some of these d-amino acids would be potential diagnostic biomarkers for Alzheimer’s disease.

Simultaneous determination of 18 d-amino acids in rat plasma

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References

  1. Kirk A, Kertesz A (1991) On drawing impairment in Alzheimer’s disease. Arch Neurol 48:73–77

    Article  CAS  Google Scholar 

  2. Pillon B, Deweer B, Aqid Y, Dubois B (1993) Explicit memory in Alzheimer’s, Huntington’s and Parkinson’s diseases. Arch Neurol 50:374–379

    Article  CAS  Google Scholar 

  3. Greene JD, Baddeley AD, Hodges JR (1996) Analysis of the episodic memory deficit in early Alzheimer’s disease: evidence from the doors and people test. Neuropsychologia 34:537–551

    Article  CAS  Google Scholar 

  4. Galton CJ, Patterson K, Xuereb JH, Hodges JR (2000) Atypical and typical presentations of Alzheimer’s disease: a clinical, neuropsychological, neuroimaging and pathological study of 13 cases. Brain 123:484–498

    Article  Google Scholar 

  5. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  Google Scholar 

  6. Friedman M (2010) Origin, microbiology, nutrition, and pharmacology of d-amino acids. Chem Biodivers 7:1491–1530

    Article  CAS  Google Scholar 

  7. Hamase K, Morikawa A, Zaitsu K (2002) D-Amino acids in mammals and their diagnostic value. J Chromatogr B 781:73–91

    Article  CAS  Google Scholar 

  8. Irukayama-Tomobe Y, Tanaka H, Yokomizo T, Hashidate-Yoshida T, Yanagisawa M, Sakurai T (2009) Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc Natl Acad Sci U S A 106:3930–3934

    Article  Google Scholar 

  9. Ohide H, Miyoshi Y, Maruyama R, Hamase K, Konno R (2011) D-Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study. J Chromatogr B 879:3162–3168

    Article  CAS  Google Scholar 

  10. Fuchs SA, Berger R, Klomp LW, de Koning TJ (2005) D-Amino acids in the central nervous system in health and disease. Mol Genet Metab 85(3):168–180

    Article  CAS  Google Scholar 

  11. Fisher GH, D'Aniello A, Vetere A, Padula L, Cusano GP, Man EH (1991) Free D-aspartate and D-alanine in normal and Alzheimer brain. Brain Res Bull 26(6):983–985

    Article  CAS  Google Scholar 

  12. Hashimoto K, Fukushima T, Shimizu E, Okada SI, Komatsu N, Okamura N, Koike K, Koizumi H, Kumakiri C, Imai K, Iyo M (2004) Possible role of d-serine in the pathophysiology of Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 28:385–388

    Article  CAS  Google Scholar 

  13. Cui Y, Jiang Z, Sun J-Y, Yu J, Li M-H, Li M-J, Liu M-X, Guo X-J (2014) Enantiomeric purity determination of (L)-amino acids with pre-column derivatization and chiral stationary phase: development and validation of the method. Food Chem 158:401–407

    Article  CAS  Google Scholar 

  14. Xie Y, Alexander GM, Schwartzman RJ, Singh N, Torjman MC, Goldberg ME, Wainer IW, Moaddel R (2014) Development and validation of a sensitive LC-MS/MS method for the determination of D-serine in human plasma. J Pharm Biomed Anal 89:1–5

    Article  CAS  Google Scholar 

  15. Guideline on bioanalytical method validation. http://www.ema.europa.eu/docs/en.GB/document−library/Scientific−guideline/2011/08/WC500109686.pdf

  16. Giuliani D, Mioni C, Altavilla D, Leone S, Bazzani C, Minutoli L, Bitto A, Cainazzo MM, Marini H, Zaffe D, Botticelli AR, Pizzala R, Savio M, Necchi D, Schiöth HB, Bertolini A, Squadrito F, Guarini S (2006) Both early and delayed treatment with melanocortin 4 receptor-stimulating melanocortins produces neuroprotection in cerebral ischemia. Endocrinology 147:1126–1135

    Article  CAS  Google Scholar 

  17. Giuliani D, Zaffe D, Ottani A, Spaccapelo L, Galantucci M, Minutoli L, Bitto A, Irrera N, Contri M, Altavilla D, Botticelli AR, Squadrito F, Guarini S (2011) Treatment of cerebral ischemia with melanocortin MC4 receptor agonists induces marked neurogenesis and long-lasting functional recovery. Acta Neuropathol 122:443–453

    Article  CAS  Google Scholar 

  18. Guidance for industry, bioanalytical method validation (updated), 2001 http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070107.pdf

  19. Mothet JP, Pollegioni L, Ouanounou G, Martineau M, Fossier P, Baux G (2005) Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc Natl Acad Sci U S A 102:5606–5611

    Article  CAS  Google Scholar 

  20. Wu J, Anwyl R, Rowan MJ (1995) beta-Amyloid selectively augments NMDA receptor-mediated synaptic transmission in rat hippocampus. Neuroreport 6:2409–2413

    Article  CAS  Google Scholar 

  21. Peng TI, Jou MJ, Sheu SS, Greenamyre JT (1998) Visualization of NMDA receptor-induced mitochondrial calcium accumulation in striatal neurons. Exp Neurol 149:1–12

    Article  CAS  Google Scholar 

  22. Mothet JP, Rouaud E, Sinet PM, Potier B, Jouvenceau A, Dutar P, Videau C, Epelbaum J, Billard JM (2006) A critical role for the glial-derived neuromodulator D-serine in the age-related deficits of cellular mechanisms of learning and memory. Aging Cell 5:267–274

    Article  CAS  Google Scholar 

  23. Wolosker H, Dumin E, Balan L, Foltyn VN (2008) D-amino acids in the brain: D-serine in neurotransmission and neurodegeneration. FEBS J 275:3514–3526

    Article  CAS  Google Scholar 

  24. Panatier A, Theodosis DT, Mothet JP, Touquet B, Polleqioni L, Poulain DA, Oliet SH (2006) Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125:775–784

    Article  CAS  Google Scholar 

  25. Billard JM (2008) D-Serine signalling as a prominent determinant of neuronal-glial dialogue in the healthy and diseased brain. J Cell Mol Med 12:1872–1884

    Article  CAS  Google Scholar 

  26. D’Aniello A, Lee JM, Petrucelli L, Di Fiore MM (1998) Regional decreases of free D-aspartate levels in Alzheimer’s disease. Neurosci Lett 250:131–134

    Article  Google Scholar 

  27. Di Maria E, Bonvicini C, Bonomini C, Alberici A, Zanetti O, Gennarelli M (2009) Genetic variation in the G720/G30 gene locus (DAOA) influences the occurrence of psychotic symptoms in patients with Alzheimer’s disease. J Alzheimers Dis 18:953–960

    Google Scholar 

  28. Boks MP, Rietkerk T, van de Beek MH, Sommer IE, de Koning TJ, Kahn RS (2007) Reviewing the role of the genes G72 and DAAO in glutamate neurotransmission in schizophrenia. Eur Neuropsychopharmacol 17:567–572

    Article  CAS  Google Scholar 

  29. Miyoshi Y, Hamase K, Okamura T, Konno R, Kasai N, Tojo Y, Zaitsu K (2011) Simultaneous two-dimensional HPLC determination of free D-serine and D-alanine in the brain and periphery of mutant rats lacking D-amino-acid oxidase. J Chromatogr B 879:3184–3189

    Article  CAS  Google Scholar 

  30. Chamond N, Cosson A, Coatnoan N, Minoprio P (2009) Proline racemases are conserved mitogens: characterization of a Trypanosoma vivax proline racemase. Mol Biochem Parasitol 165:170–179

    Article  CAS  Google Scholar 

  31. Hamase K, Takagi S, Morikawa A, Konno R, Niwa A, Zaitsu K (2006) Presence and origin of large amounts of D-proline in the urine of mutant mice lacking D-amino acid oxidase activity. Anal Bioanal Chem 386:705–711

    Article  CAS  Google Scholar 

  32. Hamase K, Inoue T, Morikawa A, Konno R, Zaitsu K (2001) Determination of free D-proline and D-leucine in the brains of mutant mice lacking D-amino acid oxidase activity. Anal Biochem 298:253–258

    Article  CAS  Google Scholar 

  33. Errico F, Napolitano F, Nisticò R, Usiello A (2012) New insights on the role of free D-aspartate in the mammalian brain. Amino Acids 43:1861–1871

    Article  CAS  Google Scholar 

  34. Billard JM (2012) D-Amino acids in brain neurotransmission and synaptic plasticity. Amino Acids 43:1851–1860

    Article  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81302735).

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Authors and Affiliations

  1. School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road Shenhe District, Shenyang, Liaoning, 110016, China

    Yuping Xing, Xiaoyan Li, Xingjie Guo & Yan Cui

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  1. Yuping Xing
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  2. Xiaoyan Li
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  3. Xingjie Guo
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  4. Yan Cui
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Correspondence to Xingjie Guo or Yan Cui.

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Xing, Y., Li, X., Guo, X. et al. Simultaneous determination of 18 d-amino acids in rat plasma by an ultrahigh-performance liquid chromatography-tandem mass spectrometry method: application to explore the potential relationship between Alzheimer’s disease and d-amino acid level alterations. Anal Bioanal Chem 408, 141–150 (2016). https://doi.org/10.1007/s00216-015-9086-3

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  • DOI: https://doi.org/10.1007/s00216-015-9086-3

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