Recent Developments in the Separation of Low Molecular Weight Heparin Anticoagulants

Author(s): Radosław Sadowski, Renata Gadzała-Kopciuch*, Bogusław Buszewski.

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 1 , 2019

  Journal Home
Translate in Chinese


The general function of anticoagulants is to prevent blood clotting and growing of the existing clots in blood vessels. In recent years, there has been a significant improvement in developing methods of prevention as well as pharmacologic and surgical treatment of thrombosis. For over the last two decades, low molecular weight heparins (LMWHs) have found their application in the antithrombotic diseases treatment. These types of drugs are widely used in clinical therapy. Despite the biological and medical importance of LMWHs, they have not been completely characterized in terms of their chemical structure. Due to both, the structural complexity of these anticoagulants and the presence of impurities, their structural characterization requires the employment of advanced analytical techniques. Since separation techniques play the key role in these endeavors, this review will focus on the presentation of recent developments in the separation of LMWH anticoagulants.

Keywords: Separation of LMWHs, liquid chromatography, ultra-high performance liquid chromatography, capillary electrophoresis, mass spectrometry, anticoagulants.

McLean, J. The thromboplactic action of cephalin. Am. J. Physiol., 1916, 41(2), 250-257.
Liu, H.; Zhang, Z.; Linhardt, R.J. Lessons learned from the contamination of heparin. Nat. Prod. Rep., 2009, 26(3), 313-321.
Rabenstein, D.L. Heparin and heparan sulfate: structure and function. Nat. Prod. Rep., 2002, 19(3), 312-331.
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.
Noti, C.; Seeberger, P.H. Chemical approaches to define the structure-activity relationship of heparin-like glycosaminoglycans. Chem. Biol., 2005, 12(7), 731-756.
Linhardt, R.J.; Liu, J. Synthetic heparin. Curr. Opin. Pharmacol., 2012, 12(2), 217-219.
Lindahl, U.; Kusche-Gullberg, M.; Kjellén, L. Regulated diversity of heparan sulfate. J. Biol. Chem., 1998, 273(39), 24979-24982.
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.
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.
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.
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.
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.
Gray, E.; Mulloy, B.; Barrowcliffe, T.W. Heparin and low-molecular-weight heparin. Thromb. Haemost., 2008, 99(5), 807-818.
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.
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.
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.
Zacharski, L.R.; Lee, A.Y.Y. Heparin as an anticancer therapeutic. Expert Opin. Investig. Drugs, 2008, 17(7), 1029-1037.
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.
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.
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.
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.
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.
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.
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.
Linhardt, R.J.; Gunay, N.S. Production and chemical processing of low molecular weight heparins. Semin. Thromb. Hemost., 1999, 25(Suppl. 3), 5-16.
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.
Mousa, S.A. The low molecular weight heparin, tinzaparin, in thrombosis and beyond. Cardiovasc. Drug Rev., 2002, 20(3), 199-216.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
USP, General Chapter. 207 “Test for 1,6-anhydro derivative for enoxaparin sodium” in the Second Supplement USP 32– NF 27 2009.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Zaia, J. On-line separations combined with MS for analysis of glycosaminoglycans. Mass Spectrom. Rev., 2009, 28(2), 254-272.
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.
Buszewski, B.; Dziubakiewicz, E.; Szumski, M. Electromigration Techniques; Berlin, Heidelberg, 2013.
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.
Mardis, E.R. Next-generation sequencing platforms. Annu. Rev. Anal. Chem. (Palo Alto, Calif.), 2013, 6(1), 287-303.
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.
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.
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.
King, J.T.; Desai, U.R. A capillary electrophoretic method for fingerprinting low molecular weight heparins. Anal. Biochem., 2008, 380(2), 229-234.
Volpi, N.; Maccari, F.; Suwan, J.; Linhardt, R.J. Electrophoresis for the analysis of heparin purity and quality. Electrophoresis, 2012, 33(11), 1531-1537.
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.
Chang, Y.; Yang, B.; Zhao, X.; Linhardt, R.J. Analysis of glycosaminoglycan-derived disaccharides by capillary electrophoresis using laser-induced fluorescence detection. Anal. Biochem., 2012, 427(1), 91-98.
Hitchcock, A.M.; Bowman, M.J.; Staples, G.O.; Zaia, J. Improved workup for glycosaminoglycan disaccharide analysis using CE with LIF detection. Electrophoresis, 2008, 29(22), 4538-4548.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Page: [166 - 176]
Pages: 11
DOI: 10.2174/0929867324666171005114150
Price: $58

Article Metrics

PDF: 24
PRC: 1