摘要
抗凝剂的一般功能是防止血液凝结和血管中现有的凝块的生长。近年来，在血栓形成的预防方法、药物治疗和外科治疗方面都取得了显著的进展。近二十年来，低分子肝素在抗血栓疾病治疗中得到了广泛的应用。这些类型的药物广泛应用于临床治疗。尽管低分子量肝素具有生物学和医学上的重要性，但其化学结构尚未完全确定。由于这两种抗凝剂的结构复杂性和杂质的存在，它们的结构表征需要采用先进的分析技术。由于分离技术在这些研究中起着关键作用，本文将重点介绍低分子肝素抗凝剂分离的最新进展。
关键词: 低分子量肝素的分离、液相色谱、超高效液相色谱、毛细管电泳、质谱、抗凝剂。
[2]
Liu, H.; Zhang, Z.; Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep., 2009, 26(3), 313-321.
[3]
Rabenstein, D.L. Heparin and heparan sulfate: structure and function. Nat. Prod. Rep., 2002, 19(3), 312-331.
[4]
Doneanu, C.E.; Chen, W.; Gebler, J.C. Analysis of oligosaccharides derived from heparin by ion-pair reversed-phase chromatography/mass spectrometry. Anal. Chem., 2009, 81(9), 3485-3499.
[5]
Noti, C.; Seeberger, P.H. Chemical approaches to define the structure-activity relationship of heparin-like glycosaminoglycans. Chem. Biol., 2005, 12(7), 731-756.
[7]
Lindahl, U.; Kusche-Gullberg, M.; Kjellén, L. Regulated diversity of heparan sulfate. J. Biol. Chem., 1998, 273(39), 24979-24982.
[8]
Chavaroche, A.A.E.; van den Broek, L.A.M.; Eggink, G. Production methods for heparosan, a precursor of heparin and heparan sulfate. Carbohydr. Polym., 2013, 93(1), 38-47.
[9]
Choay, J.; Petitou, M.; Lormeau, J.C.; Sinaÿ, P.; Casu, B.; Gatti, G. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem. Biophys. Res. Commun., 1983, 116(2), 492-499.
[10]
Ye, F.; Kuang, Y.; Chen, S.; Zhang, C.; Chen, Y.; Xing, X-H. Characteristics of low molecular weight heparin production by an ultrafiltration membrane bioreactor using maltose binding protein fused heparinase I. Biochem. Eng. J., 2009, 46(2), 193-198.
[11]
Xiao, Z.; Tappen, B.R.; Ly, M.; Zhao, W.; Canova, L.P.; Guan, H.; Linhardt, R.J. Heparin mapping using heparin lyases and the generation of a novel low molecular weight heparin. J. Med. Chem., 2011, 54(2), 603-610.
[12]
Boneu, B. Low molecular weight heparins: are they superior to unfractionated heparins to prevent and to treat deep vein thrombosis? Thromb. Res., 2000, 100(2), V113-V120.
[13]
Gray, E.; Mulloy, B.; Barrowcliffe, T.W. Heparin and low-molecular-weight heparin. Thromb. Haemost., 2008, 99(5), 807-818.
[14]
Lewis, E.J.; Xu, X. Abnormal glomerular permeability characteristics in diabetic nephropathy: implications for the therapeutic use of low-molecular weight heparin. Diabetes Care, 2008, 31(Suppl. 2), S202-S207.
[15]
Sain, M.; Kovacic, V.; Radic, J.; Ljutic, D.; Jelicic, I. Potential beneficial effects of low molecular weight heparin on cognitive impairment in elderly patients on haemodialysis. Drugs Aging, 2012, 29(1), 1-7.
[16]
Mousa, S.A.; Mohamed, S. Anti-angiogenic mechanisms and efficacy of the low molecular weight heparin, tinzaparin: anti-cancer efficacy. Oncol. Rep., 2004, 12(4), 683-688.
[17]
Zacharski, L.R.; Lee, A.Y.Y. Heparin as an anticancer therapeutic. Expert Opin. Investig. Drugs, 2008, 17(7), 1029-1037.
[18]
Ma, Q.; Cornelli, U.; Hanin, I.; Jeske, W.P.; Linhardt, R.J.; Walenga, J.M.; Fareed, J.; Lee, J.M. Heparin oligosaccharides as potential therapeutic agents in senile dementia. Curr. Pharm. Des., 2007, 13(15), 1607-1616.
[19]
Walenga, J.M.; Lyman, G.H. Evolution of heparin anticoagulants to ultra-low-molecular-weight heparins: a review of pharmacologic and clinical differences and applications in patients with cancer. Crit. Rev. Oncol. Hematol., 2013, 88(1), 1-18.
[20]
Petitou, M.; van Boeckel, C.A.A. A synthetic antithrombin III binding pentasaccharide is now a drug! What comes next? Angew. Chem. Int. Ed. Engl., 2004, 43(24), 3118-3133.
[21]
Planès, A. Review of bemiparin sodium--a new second-generation low molecular weight heparin and its applications in venous thromboembolism. Expert Opin. Pharmacother., 2003, 4(9), 1551-1561.
[22]
Xu, Y.; Masuko, S.; Takieddin, M.; Xu, H.; Liu, R.; Jing, J.; Mousa, S.A.; Linhardt, R.J.; Liu, J. Chemoenzymatic synthesis of homogeneous ultralow molecular weight heparins. Science, 2011, 334(6055), 498-501.
[23]
Maddineni, J.; Walenga, J.M.; Jeske, W.P.; Hoppensteadt, D.A.; Fareed, J.; Wahi, R.; Bick, R.L. Product individuality of commercially available low-molecular-weight heparins and their generic versions: therapeutic implications. Clin. Appl. Thromb. Hemost., 2006, 12(3), 267-276.
[24]
Hirsh, J.; Warkentin, T.E.; Shaughnessy, S.G.; Anand, S.S.; Halperin, J.L.; Raschke, R.; Granger, C.; Ohman, E.M.; Dalen, J.E. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest, 2001, 119(1)(Suppl.), 64S-94S.
[25]
Linhardt, R.J.; Gunay, N.S. Production and chemical processing of low molecular weight heparins. Semin. Thromb. Hemost., 1999, 25(Suppl. 3), 5-16.
[26]
Li, L.; Zhang, F.; Zaia, J.; Linhardt, R.J. Top-down approach for the direct characterization of low molecular weight heparins using LC-FT-MS. Anal. Chem., 2012, 84(20), 8822-8829.
[27]
Mousa, S.A. The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc. Drug Rev., 2002, 20(3), 199-216.
[28]
Wu, J.; Zhang, C.; Mei, X.; Li, Y.; Xing, X.H. Controllable production of low molecular weight heparins by combinations of heparinase I/II/III. Carbohydr. Polym., 2014, 101, 484-492.
[29]
Fu, L.; Zhang, F.; Li, G.; Onishi, A.; Bhaskar, U.; Sun, P.; Linhardt, R.J. Structure and activity of a new low-molecular-weight heparin produced by enzymatic ultrafiltration. J. Pharm. Sci., 2014, 103(5), 1375-1383.
[30]
Higashi, K.; Hosoyama, S.; Ohno, A.; Masuko, S.; Yang, B.; Sterner, E.; Wang, Z.; Linhardt, R.J.; Toida, T. Photochemical Preparation of a Novel Low Molecular Weight Heparin. Carbohydr. Polym., 2012, 67(2), 1737-1743.
[31]
Achour, O.; Bridiau, N.; Godhbani, A.; Le Joubioux, F.; Bordenave Juchereau, S.; Sannier, F.; Piot, J-M.; Fruitier Arnaudin, I.; Maugard, T. Ultrasonic-assisted preparation of a low molecular weight heparin (LMWH) with anticoagulant activity. Carbohydr. Polym., 2013, 97(2), 684-689.
[32]
Li, G.; Steppich, J.; Wang, Z.; Sun, Y.; Xue, C.; Linhardt, R.J.; Li, L. Bottom-up low molecular weight heparin analysis using liquid chromatography-Fourier transform mass spectrometry for extensive characterization. Anal. Chem., 2014, 86(13), 6626-6632.
[33]
Thanawiroon, C.; Linhardt, R.J. Separation of a complex mixture of heparin-derived oligosaccharides using reversed-phase high-performance liquid chromatography. J. Chromatogr. A, 2003, 1014(1-2), 215-223.
[34]
Zhang, F.; Yang, B.; Ly, M.; Solakyildirim, K.; Xiao, Z.; Wang, Z.; Beaudet, J.M.; Torelli, A.Y.; Dordick, J.S.; Linhardt, R.J. Structural characterization of heparins from different commercial sources. Anal. Bioanal. Chem., 2011, 401(9), 2793-2803.
[35]
Wang, Z.; Li, D.; Sun, X.; Bai, X.; Jin, L.; Chi, L. Liquid chromatography-diode array detection-mass spectrometry for compositional analysis of low molecular weight heparins. Anal. Biochem., 2014, 451, 35-41.
[36]
Patel, R.P.; Narkowicz, C.; Jacobson, G.A. Effective reversed-phase ion pair high-performance liquid chromatography method for the separation and characterization of intact low-molecular-weight heparins. Anal. Biochem., 2009, 387(1), 113-121.
[37]
Langeslay, D.J.; Urso, E.; Gardini, C.; Naggi, A.; Torri, G.; Larive, C.K. Reversed-phase ion-pair ultra-high-performance-liquid chromatography-mass spectrometry for fingerprinting low-molecular-weight heparins. J. Chromatogr. A, 2013, 1292, 201-210.
[38]
Wang, B.; Buhse, L.F.; Al-Hakim, A.; Boyne Ii, M.T.; Keire, D.A. Characterization of currently marketed heparin products: analysis of heparin digests by RPIP-UHPLC-QTOF-MS. J. Pharm. Biomed. Anal., 2012, 67-68, 42-50.
[39]
Seo, Y.; Andaya, A.; Leary, J.A. Preparation, separation, and conformational analysis of differentially sulfated heparin octasaccharide isomers using ion mobility mass spectrometry. Anal. Chem., 2012, 84(5), 2416-2423.
[40]
Ouyang, Y.; Zeng, Y.; Rong, Y.; Song, Y.; Shi, L.; Chen, B.; Yang, X.; Xu, N.; Linhardt, R.J.; Zhang, Z. Profiling analysis of low molecular weight heparins by multiple heart-cutting two dimensional chromatography with quadruple time-of-flight mass spectrometry. Anal. Chem., 2015, 87(17), 8957-8963.
[41]
Zhang, Q.; Chen, X.; Zhu, Z.; Zhan, X.; Wu, Y.; Song, L.; Kang, J. Structural analysis of low molecular weight heparin by ultraperformance size exclusion chromatography/time of flight mass spectrometry and capillary zone electrophoresis. Anal. Chem., 2013, 85(3), 1819-1827.
[42]
Fu, L.; Li, G.; Yang, B.; Onishi, A.; Li, L.; Sun, P.; Zhang, F.; Linhardt, R.J. Structural characterization of pharmaceutical heparins prepared from different animal tissues. J. Pharm. Sci., 2013, 102(5), 1447-1457.
[43]
Ouyang, Y.; Wu, C.; Sun, X.; Liu, J.; Linhardt, R.J.; Zhang, Z. Development of hydrophilic interaction chromatography with quadruple time-of-flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis. Rapid Commun. Mass Spectrom., 2016, 30(2), 277-284.
[44]
Patel, R.P.; Narkowicz, C.; Hutchinson, J.P.; Hilder, E.F.; Jacobson, G.A. A simple capillary electrophoresis method for the rapid separation and determination of intact low molecular weight and unfractionated heparins. J. Pharm. Biomed. Anal., 2008, 46(1), 30-35.
[45]
Sun, X.; Lin, L.; Liu, X.; Zhang, F.; Chi, L.; Xia, Q.; Linhardt, R.J. Capillary Electrophoresis-Mass Spectrometry for the Analysis of Heparin Oligosaccharides and Low Molecular Weight Heparin. Anal. Chem., 2016, 88(3), 1937-1943.
[46]
Rice, K.G.; Linhardt, R.J. Study of structurally defined oligosaccharide substrates of heparin and heparan monosulfate lyases. Carbohydr. Res., 1989, 190(2), 219-233.
[47]
Linhardt, R.J.; Rice, K.G.; Kim, Y.S.; Lohse, D.L.; Wang, H.M.; Loganathan, D. Mapping and quantification of the major oligosaccharide components of heparin. Biochem. J., 1988, 254(3), 781-787.
[48]
Hileman, R.E.; Smith, A.E.; Toida, T.; Linhardt, R.J. Preparation and structure of heparin lyase-derived heparan sulfate oligosaccharides. Glycobiology, 1997, 7(2), 231-239.
[49]
Chuang, W.L.; McAllister, H.; Rabenstein, L. Chromatographic methods for product-profile analysis and isolation of oligosaccharides produced by heparinase-catalyzed depolymerization of heparin. J. Chromatogr. A, 2001, 932(1-2), 65-74.
[50]
Guerrini, M.; Elli, S.; Gaudesi, D.; Torri, G.; Casu, B.; Mourier, P.; Herman, F.; Boudier, C.; Lorenz, M.; Viskov, C. Effects on molecular conformation and anticoagulant activities of 1,6-anhydrosugars at the reducing terminal of antithrombin-binding octasaccharides isolated from low-molecular-weight heparin enoxaparin. J. Med. Chem., 2010, 53(22), 8030-8040.
[51]
Vivès, R.R.; Goodger, S.; Pye, D.A. Combined strong anion-exchange HPLC and PAGE approach for the purification of heparan sulphate oligosaccharides. Biochem. J., 2001, 354(Pt 1), 141-147.
[52]
USP, General Chapter. 207 “Test for 1,6-anhydro derivative for enoxaparin sodium” in the Second Supplement USP 32– NF 27 2009.
[53]
Mourier, P.A.; Viskov, C. Chromatographic analysis and sequencing approach of heparin oligosaccharides using cetyltrimethylammonium dynamically coated stationary phases. Anal. Biochem., 2004, 332(2), 299-313.
[54]
Kitagawa, H.; Kinoshita, A.; Sugahara, K. Microanalysis of glycosaminoglycan-derived disaccharides labeled with the fluorophore 2-aminoacridone by capillary electrophoresis and high-performance liquid chromatography. Anal. Biochem., 1995, 232(1), 114-121.
[55]
Kinoshita, A.; Sugahara, K. Microanalysis of glycosaminoglycan-derived oligosaccharides labeled with a fluorophore 2-aminobenzamide by high-performance liquid chromatography: application to disaccharide composition analysis and exosequencing of oligosaccharides. Anal. Biochem., 1999, 269(2), 367-378.
[56]
Volpi, N. High-performance liquid chromatography and on-line mass spectrometry detection for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized with 2-aminoacridone. Anal. Biochem., 2010, 397(1), 12-23.
[57]
Lamari, F.; Theocharis, A.; Hjerpe, A.; Karamanos, N.K. Ultrasensitive capillary electrophoresis of sulfated disaccharides in chondroitin/dermatan sulfates by laser-induced fluorescence after derivatization with 2-aminoacridone. J. Chromatogr. B Biomed. Sci. Appl., 1999, 730(1), 129-133.
[58]
Oonuki, Y.; Yoshida, Y.; Uchiyama, Y.; Asari, A. Application of fluorophore-assisted carbohydrate electrophoresis to analysis of disaccharides and oligosaccharides derived from glycosaminoglycans. Anal. Biochem., 2005, 343(2), 212-222.
[59]
Kotani, N.; Takasaki, S. Analysis of 2-aminobenzamide-labeled oligosaccharides by high-pH anion-exchange chromatography with fluorometric detection. Anal. Biochem., 1998, 264(1), 66-73.
[60]
Grey, C.; Edebrink, P.; Krook, M.; Jacobsson, S.P. Development of a high performance anion exchange chromatography analysis for mapping of oligosaccharides. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2009, 877(20-21), 1827-1832.
[61]
Toyoda, H.; Yamamoto, H.; Ogino, N.; Toida, T.; Imanari, T. Rapid and sensitive analysis of disaccharide composition in heparin and heparan sulfate by reversed-phase ion-pair chromatography on a 2 μm porous silica gel column. J. Chromatogr. A, 1999, 830(1), 197-201.
[62]
Karamanos, N.K.; Vanky, P.; Tzanakakis, G.N.; Tsegenidis, T.; Hjerpe, A. Ion-pair high-performance liquid chromatography for determining disaccharide composition in heparin and heparan sulphate. J. Chromatogr. A, 1997, 765(2), 169-179.
[63]
Jones, C.J.; Beni, S.; Larive, C.K. Understanding the effect of the counterion on the reverse-phase ion-pair high-performance liquid chromatography (RPIP-HPLC) resolution of heparin-related saccharide anomers. Anal. Chem., 2011, 83(17), 6762-6769.
[64]
Alekseeva, A.; Casu, B.; Torri, G.; Pierro, S.; Naggi, A. Profiling glycol-split heparins by high-performance liquid chromatography/mass spectrometry analysis of their heparinase-generated oligosaccharides. Anal. Biochem., 2013, 434(1), 112-122.
[65]
Brustkern, A.M.; Buhse, L.F.; Nasr, M.; Al-Hakim, A.; Keire, D.A. Characterization of currently marketed heparin products: reversed-phase ion-pairing liquid chromatography mass spectrometry of heparin digests. Anal. Chem., 2010, 82(23), 9865-9870.
[66]
Kuberan, B.; Lech, M.; Zhang, L.; Wu, Z.L.; Beeler, D.L.; Rosenberg, R.D. Analysis of heparan sulfate oligosaccharides with ion pair-reverse phase capillary high performance liquid chromatography-microelectrospray ionization time-of-flight mass spectrometry. J. Am. Chem. Soc., 2002, 124(29), 8707-8718.
[67]
Galeotti, F.; Volpi, N. Online reverse phase-high-performance liquid chromatography-fluorescence detection-electrospray ionization-mass spectrometry separation and characterization of heparan sulfate, heparin, and low-molecular weight-heparin disaccharides derivatized with 2-aminoacridone. Anal. Chem., 2011, 83(17), 6770-6777.
[68]
Volpi, N. High-performance liquid chromatography and on-line mass spectrometry detection for the analysis of chondroitin sulfates/hyaluronan disaccharides derivatized with 2-aminoacridone. Anal. Biochem., 2010, 397(1), 12-23.
[69]
Galeotti, F.; Volpi, N. Novel reverse-phase ion pair-high performance liquid chromatography separation of heparin, heparan sulfate and low molecular weight-heparins disaccharides and oligosaccharides. J. Chromatogr. A, 2013, 1284, 141-147.
[70]
Li, D.; Chi, L.; Jin, L.; Xu, X.; Du, X.; Ji, S.; Chi, L. Mapping of low molecular weight heparins using reversed phase ion pair liquid chromatography-mass spectrometry. Carbohydr. Polym., 2014, 99, 339-344.
[71]
Thanawiroon, C.; Rice, K.G.; Toida, T.; Linhardt, R.J. Liquid chromatography/mass spectrometry sequencing approach for highly sulfated heparin-derived oligosaccharides. J. Biol. Chem., 2004, 279(4), 2608-2615.
[72]
Li, G.; Yang, B.; Li, L.; Zhang, F.; Xue, C.; Linhardt, R.J. Analysis of 3-O-sulfo group-containing heparin tetrasaccharides in heparin by liquid chromatography-mass spectrometry. Anal. Biochem., 2014, 455, 3-9.
[73]
Chai, W.; Luo, J.; Lim, C.K.; Lawson, A.M. Characterization of heparin oligosaccharide mixtures as ammonium salts using electrospray mass spectrometry. Anal. Chem., 1998, 70(10), 2060-2066.
[74]
Abzalimov, R.R.; Dubin, P.L.; Kaltashov, I.A. Glycosaminoglycans as naturally occurring combinatorial libraries: developing a mass spectrometry-based strategy for characterization of anti-thrombin interaction with low molecular weight heparin and heparin oligomers. Anal. Chem., 2007, 79(16), 6055-6063.
[75]
Zamfir, A.; Seidler, D.G.; Schönherr, E.; Kresse, H.; Peter-Katalinić, J. On-line sheathless capillary electrophoresis/nanoelectrospray ionization-tandem mass spectrometry for the analysis of glycosaminoglycan oligosaccharides. Electrophoresis, 2004, 25(13), 2010-2016.
[76]
Laremore, T.N.; Linhardt, R.J. Improved matrix-assisted laser desorption/ionization mass spectrometric detection of glycosaminoglycan disaccharides as cesium salts. Rapid Commun. Mass Spectrom., 2007, 21(7), 1315-1320.
[77]
Laremore, T.N.; Murugesan, S.; Park, T.J.; Avci, F.Y.; Zagorevski, D.V.; Linhardt, R.J. Matrix-assisted laser desorption/ionization mass spectrometric analysis of uncomplexed highly sulfated oligosaccharides using ionic liquid matrices. Anal. Chem., 2006, 78(6), 1774-1779.
[78]
Pope, R.M.; Raska, C.S.; Thorp, S.C.; Liu, J. Analysis of heparan sulfate oligosaccharides by nano-electrospray ionization mass spectrometry. Glycobiology, 2001, 11(6), 505-513.
[79]
Solakyildirim, K.; Zhang, Z.; Linhardt, R.J. Ultraperformance liquid chromatography with electrospray ionization ion trap mass spectrometry for chondroitin disaccharide analysis. Anal. Biochem., 2010, 397(1), 24-28.
[80]
Xu, X.; Li, D.; Chi, L.; Du, X.; Bai, X.; Chi, L. Fragment profiling of low molecular weight heparins using reversed phase ion pair liquid chromatography-electrospray mass spectrometry. Carbohydr. Res., 2015, 407, 26-33.
[81]
Li, H.; Wickramasekara, S.; Nemes, P. One-hour screening of adulterated heparin by simplified peroxide digestion and fast RPIP-LC-MS(2). Anal. Chem., 2015, 87(16), 8424-8432.
[82]
Yang, B.; Weyers, A.; Baik, J.Y.; Sterner, E.; Sharfstein, S.; Mousa, S.A.; Zhang, F.; Dordick, J.S.; Linhardt, R.J. Ultra-performance ion-pairing liquid chromatography with on-line electrospray ion trap mass spectrometry for heparin disaccharide analysis. Anal. Biochem., 2011, 415(1), 59-66.
[83]
Noga, S.; Bocian, S.; Buszewski, B. Hydrophilic interaction liquid chromatography columns classification by effect of solvation and chemometric methods. J. Chromatogr. A, 2013, 1278, 89-97.
[84]
Takegawa, Y.; Araki, K.; Fujitani, N.; Furukawa, J.; Sugiyama, H.; Sakai, H.; Shinohara, Y. Simultaneous analysis of heparan sulfate, chondroitin/dermatan sulfates, and hyaluronan disaccharides by glycoblotting-assisted sample preparation followed by single-step zwitter-ionic-hydrophilic interaction chromatography. Anal. Chem., 2011, 83(24), 9443-9449.
[85]
Zaia, J. On-line separations combined with MS for analysis of glycosaminoglycans. Mass Spectrom. Rev., 2009, 28(2), 254-272.
[86]
Szumski, M.; Kłodzińska, E.; Dziubakiewicz, E.; Hrynkiewicz, K.; Buszewski, B. Effect of applied voltage on viability of bacteria during separation under electrophoretic conditions. J. Liq. Chromatogr. Relat. Technol., 2011, 34(20), 2689-2698.
[87]
Buszewski, B.; Dziubakiewicz, E.; Szumski, M. Electromigration Techniques; Berlin, Heidelberg, 2013.
[88]
Calcerrada, M.; González-Herráez, M.; García-Ruiz, C. Recent advances in capillary electrophoresis instrumentation for the analysis of explosives. TrAC Trends in Analytical Chemistry, 2016, 75, 75-85.
[89]
Mardis, E.R. Next-generation sequencing platforms. Annu. Rev. Anal. Chem. (Palo Alto, Calif.), 2013, 6(1), 287-303.
[90]
Ucakturk, E.; Cai, C.; Li, L.; Li, G.; Zhang, F.; Linhardt, R.J. Capillary electrophoresis for total glycosaminoglycan analysis. Anal. Bioanal. Chem., 2014, 406(19), 4617-4626.
[91]
Militsopoulou, M.; Lamari, F.N.; Hjerpe, A.; Karamanos, N.K. Determination of twelve heparin- and heparan sulfate-derived disaccharides as 2-aminoacridone derivatives by capillary zone electrophoresis using ultraviolet and laser-induced fluorescence detection. Electrophoresis, 2002, 23(7-8), 1104-1109.
[92]
Volpi, N.; Maccari, F.; Linhardt, R.J. Quantitative capillary electrophoresis determination of oversulfated chondroitin sulfate as a contaminant in heparin preparations. Anal. Biochem., 2009, 388(1), 140-145.
[93]
King, J.T.; Desai, U.R. A capillary electrophoretic method for fingerprinting low molecular weight heparins. Anal. Biochem., 2008, 380(2), 229-234.
[94]
Volpi, N.; Maccari, F.; Suwan, J.; Linhardt, R.J. Electrophoresis for the analysis of heparin purity and quality. Electrophoresis, 2012, 33(11), 1531-1537.
[95]
Militsopoulou, M.; Lecomte, C.; Bayle, C.; Couderc, F.; Karamanos, N.K. Laser-induced fluorescence as a powerful detection tool for capillary electrophoretic analysis of heparin/heparan sulfate disaccharides. Biomed. Chromatogr., 2003, 17(1), 39-41.
Related Journals
Current Pharmaceutical Design
Current Topics in Medicinal Chemistry
Current Respiratory Medicine Reviews
Infectious Disorders - Drug Targets
Endocrine, Metabolic & Immune Disorders - Drug Targets
Anti-Infective Agents
Coronaviruses
Recent Advances in Inflammation & Allergy Drug Discovery
Current Probiotics
Article Metrics
40
4
1