Abstract：OBJECTIVE To establish a method for analysis of related substances in biapenem with micellar electrokinetic capillary chromatography(MEKC). METHODS In order to improve the separation selectivity, a zwitterionic surfactant, 3-(N,N-dimethylhexadecylammonium)-propanesulfonate(PAPS) was used. The optimal separation conditions were as follows: the total length of the capillary was 48.5 cm (the effective length was 48 cm), the buffer was 90 mmol·L-1 tris(hydroxymethyl)aminomethane (tris)-phosphate buffer containing 17 mmol·L-1 PAPS and 3 mg·mL-1 polyoxyethylene 23 lauryl ether (Brij 35), the applied voltage was 22 kV, and the capillary temperature was controlled at 30 ℃. Further more,the specificity, linearity, precision, repeatability, stability and durability were studied. The contents of related substances in biapenem commercial samples were analyzed. RESULTS The MEKC method, which was a comparable analysis method to HPLC, successfully separated the adjacent impurities of biapenem by using the zwitterionic surfactant PAPS. The specific test showed that this method was especially suitable for the detection of biapenem dimers A, B and open-ring compound. CONCLUSION In this method, MEKC with zwitterionic surfactant is for the first time applied to the analysis of related substances in biapenem (amphoteric drugs). It provides a feasible analysis method with high sensitivity, good specificity and reproducibility for the quality control of biapenem.
张含智,李敏, 罗文燕, 丁颖, 刘浩. 胶束电动毛细管电泳法分析比阿培南中的有关物质[J]. 中国药学杂志, 2020, 55(16): 1367-1371.
ZHANG Han-zhi, LI Min, LUO Wen-yan, DING Ying, LIU Hao. Analysis of Related Substances in Biapenam by Micellar Electrokinetic Capillary Chromatography. Chinese Pharmaceutical Journal, 2020, 55(16): 1367-1371.
BONFIGLIO G, MACCARONE G, MEZZATESTA M L, et al. In vitro activity biapenem against recent gram-negative and gram-positive clinical isolates. Chemotherapy, 1997, 43(6): 393-399.
ZHENG M J, MA S T. Research progress on the relationship between structure and activity of carbapenem antibiotics. Chin Pharm J(中国药学杂志), 2007, 42(22): 1681-1685.
JIA Y H, XING W W. Advance in the quality research of biapenem for injection. Chin J New Drugs(中国新药杂志), 2013, 22(11): 1285-1288.
LIU J H, ZHANG L, CHNEG Y B, et al. HPLC determination of biapenem dimer and study on its degradation pathways. Chin J Pharm Anal(药物分析杂志), 2012, 32(3): 468-472.
CHEN S J, WANG D G, ZHANG L, et al. Identification of biapenem opening ring impurities and content determination of them. J China Pharm(中国药房), 2014, 24(41): 3915-3918.
ZHANG J, XING L B. Content and relative substances determination of biapenem for injection by HPLC. Chin J Antibiot(中国抗生素杂志), 2006, 31(9): 565-566.
JI Y M, WU S M, ZHANG Y L, et al. Determination of polymerized impurities in biapenem by HPSEC. Chin J Antibiot(中国抗生素杂志), 2015, 40(1): 51-55.
XIA M, HANG T J, ZHANG F, et al. The stability of biapenem and structural identification of impurities in aqueous solution. J Pharm Biomed Anal, 2009, 49(4): 937-944.
WANG N, LI C F, ZHANG D S, et al. Establishment of an HPLC method for the analysis of biapenem and its impurities. J Chin Pharm Sci, 2011, 20(2): 171-180. MICHALSKA K, CIELECKA P J, PAJCHEL G, et al. Determination of biapenem in a medicinal product by micellar electrokinetic chromatography with sweeping in an enhanced electric field. J Chromatogr A, 2013, 1282: 153-160. LIU H, HU C Q, QIU S L. Analysis of norvancomycin hydrochloric acid by high performance liquid chromatography and micellar electrokinetic capillary chromatography. Chin J Antibiot(中国抗生素杂志), 2004, 29(10): 592-597. KRISTENSEN H K, HANSEN S H. Separation of polymyxins by micellar electrokinetic capillary chromatography. J Chromatogr A, 1993, 628(2): 309-315. ZHANG H Z, QIN F, XU X X, et al. Determination of related substances in polymyxin B sulfate by capillary electrophoresis. Chin J Antibiot(中国抗生素杂志), 2019, 44(4): 450-454. KANG J W, SCHEPDAEL A V, HOOGMARTENS J, et al. Analysis of bacitracin by micellar electrokinetic capillary chromatography with mixed micelle in acid solution. Electrophoresis, 2001, 22(7): 1356-1362.