Capillary electrophoresis (CE) shows remarkable separation performance and has advanced to a mature technique for all aspects of pharmaceutical analysis. In this study, triangle coupled with tetrahedron optimization method was used to develope a simple CE method for establishing the CE fingerprints of Alkaloids of Sophora flavescens (ASF). Computer-aided molecular modeling study was first performed to investigate the separation mechanism of the diastereomers in ASF. Experimental results and molecular modeling studies both support that significant differences in the complexation stabilities of the alkaloids with borate and citric acid is mainly responsible for the separation of matrine and sophoridine.

Hou Zhifei. Exploration of Capillary Electrophoresis Separation Mechanism for Alkaloids of Sophora Flavescens by Computer-aided Molecular Modeling. Frontiers in Medical Science Research(2025), Vol. 7, Issue 2: 97-102. https://doi.org/10.25236/FMSR.2025.070214.

[1] The State Commission of Chinese Pharmacopoeia. The State Drug Standard: Local standard for chemical products increased national standard, Vol. 12. People’s Medical Publishing House. 2002, pp. 27.

[2] Zhang X, Cui Z, Wang D, Zhou H, High performance liquid chromatographic fingerprint evaluation of the quinolizidine alkaloids from commercial Radix Sophorae Flavescentis [J]. J Asian Nat Prod Res. 2003, 5: 171-182. 

[3] Wang H, Lu Y, Chen J, Li J, Liu S, Subcritical water extraction of alkaloids in Sophora flavescens Ait. and determination by capillary electrophoresis with field-amplified sample stacking [J]. J Pharmaceut Biomed. 2012, 58: 146-151. 

[4] Lorenz H, Seidel-Morgenstern A, Processes To Separate Enantiomers [J]. Angew Chem Int Edit. 2014, 53: 1218–1250.

[5] Zhang H, Li Q, Mao L, Chen Y, Chiral separation using capillary electromigration techniques based on ligand exchange principle [J]. J. Sep. Sci. 2012, 35: 1236-1248.

[6] Aizawa S, Yamamoto A, Kodama S, Mechanism of enantioseparation of DL-pantothenic acid in ligand exchange capillary electrophoresis using a diol-borate system[J]. Electrophoresis. 2006, 27: 880-886.

[7] Furlanetto S,  Orlandini S, Pasquini B, Caprini C, Mura P, Pinzauti S, Fast analysis of glibenclamide and its impurities: quality by design framework in capillary electrophoresis method development [J]. Anal Bioanal Chem. 2015, 407: 7637-7646.

[8] Sun G, Hu Y, Bi K, Evaluating the quality of Niuhuangjiedu tablets by the systematic quantified fingerprint method [J]. Acta Pharmaceutica Sinica. 2009, 44: 401-405.

[9] Yang W, Wang G, Li P, Zhou R, Determination of the Ionization Constant of matrine by the Spectrophotometric Indicator Method [J]. J Shenyang Pharm Univ. 1992, 9: 297-298.

[10] Du S, Deng Y, Liang W, Physicochemical properties study of oxymatrine [J]. J Shenyang Pharm Univ. 2006, 23: 80-83.

[11] Wang G, Yang B, Liu Y, Li P, Liu Z, Determination of the Ionization Constant of Sophoridine by the Spectrophotometric Indicator Method [J]. J Shenyang Pharm Univ. 2000, 17: 424-426.

[12] Famer J, Advances in Inorganic Chemistry and Radiochemistry [J]. Metal Borates. 1982, 25: 187-225.

[13] Zhou Y, Fang C, Fang Y, Zhu F, Polyborates in aqueous borate solution: A Raman and DFT theory investigation [J]. Spectrochim Acta A Mol Biomol Spectrosc. 2011, 83: 82-87.

[14] Zhu F, Fang C, Fang Y, Zhou Y, Xu S, Tao S, Cao L, Structure of Aqueous Potassium Tetraborate Solutions [J]. Acta Chimica Sinica. 2012, 70: 445-452.

[15] Shen G, Peng Z, Huang H, Shi Y, Yu A, Jin Q, Studies on Separation of Different Species Containing Boron in Boric Acid Solution Using Electrostatic Ion Chromatography [J]. Chem Res Chinese U. 1999, 20: 1538-1541.

[16] Momii R, Nachtrieb N, Nuclear Magnetic Resonance Study of Borate-Polyborate Equilibria in Aqueous Solution [J]. Inorganic Chemistry. 1967, 6: 1189-1192.

[17] Suliman F, Elbashir A, Enantiodifferentiation of chiral baclofen by b-cyclodextrin using capillary electrophoresis: A molecular modeling approach [J]. J Mol Struct. 2012, 1019: 43-49.