Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.
[en] The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of abundant l-AAs.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Crommen, Jacques ; Université de Liège > Département de pharmacie > Département de pharmacie
Servais, Anne-Catherine ; Université de Liège > Département de pharmacie > Analyse des médicaments
Fillet, Marianne ; Université de Liège > Département de pharmacie > Analyse des médicaments
de Jong, G. J.
Somsen, G. W.
Language :
English
Title :
Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.
Publication date :
2016
Journal title :
Analytica Chimica Acta
ISSN :
0003-2670
eISSN :
1873-4324
Publisher :
Elsevier, Netherlands
Volume :
940
Pages :
150-8
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2016 Elsevier B.V. All rights reserved.
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Bibliography
[1] Bruckner, H., Schieber, A., Ascertainment of D-amino acids in germ-free, gnotobiotic and normal laboratory rats. Biomed. Chromatogr. 15 (2001), 257–262.
[2] Young, G.A., Kendall, S., Brownjohn, A.M., D-Amino acids in chronic renal failure and the effects of dialysis and urinary losses. Amino Acids 6 (1994), 283–293.
[3] Miyoshi, Y., Hamase, K., Tojo, Y., Mita, M., Konno, R., Zaitsu, K., Determination of D-serine and D-alanine in the tissues and physiological fluids of mice with various D-amino-acid oxidase activities using two-dimensional high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 877 (2009), 2506–2512.
[4] Morikawa, A., Hamase, K., Zaitsu, K., Determination of D-alanine in the rat central nervous system and periphery using column-switching high-performance liquid chromatography. Anal. Biochem. 312 (2003), 66–72.
[5] Ohide, H., Miyoshi, Y., Maruyama, R., Hamase, K., Konno, R., D-Amino acid metabolism in mammals: biosynthesis, degradation and analytical aspects of the metabolic study. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (2011), 3162–3168.
[6] Nishikawa, T., Analysis of free D-serine in mammals and its biological relevance. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (2011), 3169–3183.
[7] Katane, M., Homma, H., D-Aspartate–an important bioactive substance in mammals: a review from an analytical and biological point of view. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 879 (2011), 3108–3121.
[8] Hamase, K., Morikawa, A., Etoh, S., Tojo, Y., Miyoshi, Y., Zaitsu, K., Analysis of small amounts of D-amino acids and the study of their physiological functions in mammals. Anal. Sci. 25 (2009), 961–968.
[9] Fuchs, S.A., Berger, R., Klomp, L.W., de Koning, T.J., D-amino acids in the central nervous system in health and disease. Mol. Genet. Metab. 85 (2005), 168–180.
[10] Kumashiro, S., Hashimoto, A., Nishikawa, T., Free d-serine in postmortem brains and spinal-cords of individuals with and without neuropsychiatric diseases. Brain Res. 681 (1995), 117–125.
[11] Fisher, G.H., Daniello, A., Vetere, A., Padula, L., Cusano, G.P., Man, E.H., Free d-aspartate and d-alanine in normal and alzheimer brain. Brain Res. Bull. 26 (1991), 983–985.
[12] Waldhier, M.C., Gruber, M.A., Dettmer, K., Oefner, P.J., Capillary electrophoresis and column chromatography in biomedical chiral amino acid analysis. Anal. Bioanal. Chem. 394 (2009), 695–706.
[13] Reischl, R.J., Lindner, W., Methoxyquinoline labeling–a new strategy for the enantioseparation of all chiral proteinogenic amino acids in 1-dimensional liquid chromatography using fluorescence and tandem mass spectrometric detection. J. Chromatogr. A 1269 (2012), 262–269.
[14] Visser, W.F., Verhoeven-Duif, N.M., Ophoff, R., Bakker, S., Klomp, L.W., Berger, R., de Koning, T.J., A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass spectrometry based method for the quantification of D-amino acids in body fluids. J. Chromatogr. A 1218 (2011), 7130–7136.
[15] Bruckner, H., Schieber, A., Determination of amino acid enantiomers in human urine and blood serum by gas chromatography-mass spectrometry. Biomed. Chromatogr. 15 (2001), 166–172.
[16] Giuffrida, A., Leon, C., Garcia-Canas, V., Cucinotta, V., Cifuentes, A., Modified cyclodextrins for fast and sensitive chiral-capillary electrophoresis-mass spectrometry. Electrophoresis 30 (2009), 1734–1742.
[17] Dominguez-Vega, E., Sanchez-Hernandez, L., Garcia-Ruiz, C., Crego, A.L., Marina, M.L., Development of a CE-ESI-ITMS method for the enantiomeric determination of the non-protein amino acid ornithine. Electrophoresis 30 (2009), 1724–1733.
[18] Simo, C., Rizzi, A., Barbas, C., Cifuentes, A., Chiral capillary electrophoresis-mass spectrometry of amino acids in foods. Electrophoresis 26 (2005), 1432–1441.
[19] Sanchez-Hernandez, L., Serra, N.S., Marina, M.L., Crego, A.L., Enantiomeric separation of free L- and d-amino acids in hydrolyzed protein fertilizers by capillary electrophoresis tandem mass spectrometry. J. Agric. Food Chem. 61 (2013), 5022–5030.
[20] Prior, A., Sanchez-Hernandez, L., Sastre-Torano, J., Marina, M.L., de Jong, G.J., Somsen, G.W., Enantioselective analysis of proteinogenic amino acids in cerebrospinal fluid by capillary electrophoresis-mass spectrometry. Electrophoresis, 2016, 10.1002/elps.201600015.
[22] Tanaka, Y., Kishimoto, Y., Terabe, S., Separation of acidic enantiomers by capillary electrophoresis mass spectrometry employing a partial filling technique. J. Chromatogr. A 802 (1998), 83–88.
[23] Rudaz, S., Cherkaoui, S., Gauvrit, J.Y., Lanteri, P., Veuthey, J.L., Experimental designs to investigate capillary electrophoresis-electrospray ionization-mass spectrometry enantioseparation with the partial-filling technique. Electrophoresis 22 (2001), 3316–3326.
[24] Tanaka, Y., Otsuka, K., Terabe, S., Separation of enantiomers by capillary electrophoresis-mass spectrometry employing a partial filling technique with a chiral crown ether. J. Chromatogr. A 875 (2000), 323–330.
[25] Xia, S., Zhang, L., Lu, M., Qiu, B., Chi, Y., Chen, G., Enantiomeric separation of chiral dipeptides by CE-ESI-MS employing a partial filling technique with chiral crown ether. Electrophoresis 30 (2009), 2837–2844.
[26] Fanali, S., Desiderio, C., Use of vancomycin as chiral selector in capillary electrophoresis. Optimization and quantitation of loxiglumide enantiomers in pharmaceuticals. Hrc J. High. Res. Chrom. 19 (1996), 322–326.
[27] Yuan, B., Wu, H., Sanders, T., McCullum, C., Zheng, Y., Tchounwou, P.B., Liu, Y.M., Chiral capillary electrophoresis-mass spectrometry of 3,4-dihydroxyphenylalanine: evidence for its enantioselective metabolism in PC-12 nerve cells. Anal. Biochem. 416 (2011), 191–195.
[28] Fanali, S., Desiderio, C., Schulte, G., Heitmeier, S., Strickmann, D., Chankvetadze, B., Blaschke, G., Chiral capillary electrophoresis electrospray mass spectrometry coupling using vancomycin as chiral selector. J. Chromatogr. A 800 (1998), 69–76.
[29] Schulte, G., Heitmeier, S., Chankvetadze, B., Blaschke, G., Chiral capillary electrophoresis electrospray mass spectrometry coupling with charged cyclodextrin derivatives as chiral selectors. J. Chromatogr. A 800 (1998), 77–82.
[30] Kindt, E.K., Kurzyniec, S., Wang, S.C., Kilby, G., Rossi, D.T., Quantitative bioanalysis of enantiomeric drugs using capillary electrophoresis and electrospray mass spectrometry. J. Pharm. Biomed. Anal. 31 (2003), 893–904.
[31] Mol, R., Servais, A.C., Fillet, M., Crommen, J., de Jong, G.J., Somsen, G.W., Nonaqueous electrokinetic chromatography-electrospray ionization mass spectrometry using anionic cyclodextrins. J. Chromatogr. A 1159 (2007), 51–57.
[32] Mol, R., de Jong, G.J., Somsen, G.W., Coupling of non-aqueous electrokinetic chromatography using cationic cyclodextrins with electrospray ionization mass spectrometry. Rapid Commun. Mass Spectrom. 22 (2008), 790–796.
[33] Tanaka, Y., Kishimoto, Y., Otsuka, K., Terabe, S., Strategy for selecting separation solutions in capillary electrophoresis mass spectrometry. J. Chromatogr. A 817 (1998), 49–57.
[34] Cherkaoui, S., Veuthey, J.L., Use of negatively charged cyclodextrins for the simultaneous enantioseparation of selected anesthetic drugs by capillary electrophoresis-mass spectrometry. J. Pharm. Biomed. Anal. 27 (2002), 615–626.
[35] Rudaz, S., Calleri, E., Geiser, L., Cherkaoui, S., Prat, J., Veuthey, J.L., Infinite enantiomeric resolution of basic compounds using highly sulfated cyclodextrin as chiral selector in capillary electrophoresis. Electrophoresis 24 (2003), 2633–2641.
[36] Vogt, C., Georgi, A., Werner, G., Enantiomeric separation of d/l-carnitine using Hplc and Cze after derivatization. Chromatographia 40 (1995), 287–295.
[37] Dewitt, P., Deias, R., Muck, S., Galletti, B., Meloni, D., Celletti, P., Marzo, A., High-performance liquid-chromatography and capillary electrophoresis of l-carnitine and d-carnitine by precolumn diastereomeric derivatization. J. Chromatogr. B Biomed. Appl. 657 (1994), 67–73.
[38] Chan, K.C., Muschik, G.M., Issaq, H.J., Enantiomeric separation of amino-acids using micellar electrokinetic chromatography after precolumn derivatization with the chiral reagent 1-(9-Fluorenyl)Ethyl chloroformate. Electrophoresis 16 (1995), 504–509.
[39] Fradi, I., Farcas, E., Said, A.B., Yans, M.L., Lamalle, C., Somsen, G.W., Prior, A., de Jong, G.J., Kallel, M., Crommen, J., Servais, A.C., Fillet, M., In-capillary derivatization with (-)-1-(9-fluorenyl)ethyl chloroformate as chiral labeling agent for the electrophoretic separation of amino acids. J. Chromatogr. A 1363 (2014), 338–347.
[40] Mol, R., de Jong, G.J., Somsen, G.W., Atmospheric pressure photoionization for enhanced compatibility in on-line micellar electrokinetic chromatography-mass spectrometry. Anal. Chem. 77 (2005), 5277–5282.
[41] Somsen, G.W., Mol, R., de Jong, G.J., On-line micellar electrokinetic chromatography-mass spectrometry: feasibility of direct introduction of non-volatile buffer and surfactant into the electrospray interface. J. Chromatogr. A 1000 (2003), 953–961.
[42] Hommerson, P., Khan, A.M., de Jong, G.J., Somsen, G.W., Capillary electrophoresis-atmospheric pressure chemical ionization-mass spectrometry using an orthogonal interface: set-up and system parameters. J. Am. Soc. Mass Spectrom. 20 (2009), 1311–1318.
[43] Petersson, P., Jornten-Karlsson, M., Stalebro, M., Direct coupling of micellar electrokinetic chromatography to mass spectrometry using a volatile buffer system based on perfluorooctanoic acid and ammonia. Electrophoresis 24 (2003), 999–1007.
[44] Van Biesen, G., Bottaro, C.S., Ammonium perfluorooctanoate as a volatile surfactant for the analysis of N-methylcarbamates by MEKC-ESI-MS. Electrophoresis 27 (2006), 4456–4468.
[45] Moreno-Gonzalez, D., Gamiz-Gracia, L., Bosque-Sendra, J.M., Garcia-Campana, A.M., Dispersive liquid-liquid microextraction using a low density extraction solvent for the determination of 17 N-methylcarbamates by micellar electrokinetic chromatography-electrospray-mass spectrometry employing a volatile surfactant. J. Chromatogr. A 1247 (2012), 26–34.
[46] Moreno-Gonzalez, D., Torano, J.S., Gamiz-Gracia, L., Garcia-Campana, A.M., de Jong, G.J., Somsen, G.W., Micellar electrokinetic chromatography-electrospray ionization mass spectrometry employing a volatile surfactant for the analysis of amino acids in human urine. Electrophoresis 34 (2013), 2615–2622.
[47] Einarsson, S., Josefsson, B., Moeller, P., Sanchez, D., Separation of amino acid enantiomers and chiral amines using precolumn derivatization with (+)-1-(9-fluorenyl)ethyl chloroformate and reversed-phase liquid chromatography. Anal. Chem. 59 (1987), 1191–1195.
[48] Okuma, E., Abe, H., Simultaneous determination of d-amino and l-amino acids in the nervous tissues of Crustaceans using precolumn derivatization with (+)-1-(9-Fluorenyl)Ethyl chloroformate and reversed-phase ion-pair high-performance liquid-chromatography. J. Chromatogr. B Biomed. Appl. 660 (1994), 243–250.
[49] Viglio, S., Fumagalli, M., Ferrari, F., Iadarola, P., MEKC: a powerful tool for the determination of amino acids in a variety of biomatrices. Electrophoresis 31 (2010), 93–104.
[50] Goss, K.-U., The pKaValues of PFOA and other highly fluorinated carboxylic acids. Environ. Sci. Technol. 42 (2008), 456–458.
[51] Wang, C., Yan, P., Xing, H., Jin, C., Xiao, J.X., Thermodynamics of aggregation of ammonium/tetraalkylammonium perfluorooctanoates: effect of counterions. J. Chem. Eng. Data 55 (2010), 1994–1999.
[52] Macia, A., Borrull, F., Calull, M., Aguilar, C., Determination of some acidic drugs in surface and sewage treatment plant waters by capillary electrophoresis-electrospray ionization-mass spectrometry. Electrophoresis 25 (2004), 3441–3449.
[53] Jambor, A., Molnar-Perl, I., Amino acid analysis by high-performance liquid chromatography after derivatization with 9-fluorenylmethyloxycarbonyl chloride Literature overview and further study. J. Chromatogr. A 1216 (2009), 3064–3077.
[54] Bank, R.A., Jansen, E.J., Beekman, B., Koppele, J.M.T., Amino acid analysis by reverse-phase high-performance liquid chromatography: improved derivatization and detection conditions with 9-fluorenylmethyl chloroformate. Anal. Biochem. 240 (1996), 167–176.
[55] Einarsson, S., Josefsson, B., Lagerkvist, S., Determination of amino-acids with 9-Fluorenylmethyl chloroformate and reversed-phase high-performance liquid-chromatography. J. Chromatogr. A 282 (1983), 609–618.
[56] http://www.labcorp.com.
[57] Fisher, G., Lorenzo, N., Abe, H., Fujita, E., Frey, W.H., Emory, C., Di Fiore, M.M., A, D.A., Free D- and L-amino acids in ventricular cerebrospinal fluid from Alzheimer and normal subjects. Amino Acids 15 (1998), 263–269.
[58] Thorsen, G., Bergquist, J., Chiral separation of amino acids in biological fluids by micellar electrokinetic chromatography with laser-induced fluorescence detection. J. Chromatogr. B Biomed. Sci. Appl. 745 (2000), 389–397.
[59] Haselberg, R., Ratnayake, C.K., de Jong, G.J., Somsen, G.W., Performance of a sheathless porous tip sprayer for capillary electrophoresis-electrospray ionization-mass spectrometry of intact proteins. J. Chromatogr. A 1217 (2010), 7605–7611.
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