目的 建立一种基于高效液相色谱-四级杆飞行时间质谱(HPLC-Q/TOF-MS)的替考拉宁组分分离和结构解析的分析方法。方法 采用Symmetry C18色谱柱,以含0.1%甲酸的水溶液为流动相A,以含0.1%甲酸的乙腈溶液为流动相B,线性梯度条件洗脱。建立了基于高分辨质谱信息的替考拉宁的结构解析策略,详细归属了替考拉宁母核离子、低相对分子质量端的脂肪酰基-氨基葡萄糖及N-乙酰基葡萄糖胺特征离子所代表的碎片结构。结果 首次系统总结了替考拉宁的裂解途径,发现了2个母核开环后的特征碎片离子。除《欧洲药典》10.0版中已收录的10个组分外,推导了11个具有替考拉宁母核的组分和4个脂肪酰基-氨基葡萄糖化合物,特别是具有不饱和脂肪酰基的组分,包括4个脂肪酰基含有双键(RS-8a、RS-8b、RS-10a和RS-10b)和1个含有共轭双键的组分(RS-6)。结论 基于高分辨质谱的结构解析策略可用于替考拉宁未知组分的结构鉴定,为严格控制替考拉宁的质量提供了一种解决思路。
Abstract
OBJECTIVE To establish a high performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (HPLC-Q/TOF-MS) method for the structural analysis of the components in teicoplanin. METHODS The analysis was performed on Agilent 1260-6550 Q/TOF-MS by a symmetry C18 column with 0.1% formic acid aqueous solution as mobile phase A and 0.1% formic acid in acetonitrile as mobile phase B under gradient elution. The strategy for structural elucidation of components in teicoplanin based on the high resolution mass data (MS and MS/MS) was established. The fragmentation structures represented by parent core ions, fatty acyl-glucosamine ions and N-acetylglucosamine ions were assigned in detail. Two ring opening fragmentation ions of teicoplanin were proposed. RESULTS Besides the ten components recorded in the European Pharmacopoeia 10.0, eleven components with the parent core of teicoplanin and four different fatty acyl-glucosamine compounds were identified. In particular, the components with unsaturated fatty chain were elucidated including four fatty acyl groups with one double bond (RS-8a, RS-8b, RS-10a and RS-10b) and one with conjugated double bond (RS-6). CONCULUSION This study provides an efficient solution to quickly determine the structures of components in teicoplanin.
关键词
替考拉宁 /
结构解析策略 /
飞行时间质谱 /
不饱和脂肪酰基
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Key words
teicoplanin /
structural elucidation strategy /
TOF/MS /
unsaturated fatty acyl
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中图分类号：
R917
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参考文献
[1] PARENTI F, BERETTA G, BERTI M, et al. Teichomycins, new antibiotics from Actinoplanes Teichomyceticus nov.sp. Ⅱ. Extraction and chemical characterization. J Antibiot, 1978, 31(4): 170-177.
[2] NICOLAOU K C, BODDY C N C, BRSE S, et al. Chemistry, Biology and medicine of the glycopeptide antibiotics. Angew Chem Int Ed, 1999, 38(15): 2096-2152.
[3] KAHNE D, LEIMKUHLER C, LU W, et al. Glycopeptide and lipoglycopeptide antibiotics. Chem Rev, 2005, 105(2): 425-448.
[4] Ch. P(2020) Vol Ⅱ (中国药典2020年版.二部). 2020: 1496-1497.
[5] EP 10.0. 2020: 3967-3970.
[6] TENGATTINI S, CORANA F, BIANCHI, et al. Application of an HPLC-MS/MS method for Teicoplanin drug substance and related impurities, part 2: Identity assignment of related impurities. J Pharm Biomed Anal, 2019, 168: 38-43.
[7] BARNA J C J, WILLIAMS D H, STONE D J M, et al. Structure elucidation of the teicoplanin antibiotics. J Am Chem Soc, 1984, 106(17): 4895-4902.
[8] COMETTI A, GALLO G G, KETTENRING J, et al. Isolation and structure determination of the main related substances of teicoplanin, a glycopeptide antibiotic. Farmaco Sci, 1988,43(12):1005-1018.
[9] BORGHI A, ANTONINI P, ZANOL M, et al. Isolation and structure determination of two new analogs of teicoplanin, a glycopeptide antibiotic. J Antibiot, 1988, 4(3): 361-366.
[10] QUARTA C, BORGHI A, ZERILLI L F, et al. Isolation and structure determination of a novel complex of the teicoplanin family. J Antibiot, 1996, 49(7): 644-650.
[11] MARRUBINI G, TENGATTINI S, COLOMBO R, et al. A new MS compatible HPLC-UV method for Teicoplanin drug substance and related impurities, part 1: Development and validation studies. J Pharm Biomed Anal, 2019, 162: 185-191.
[12] GARCA-GMEZ D, DAZ B A, RODRGUEZ-GONZALO E. LC-HRMS based on mixed-mode chromatography for the separation of teicoplanin and the unravelment of its composition. J Pharm Biomed Anal, 2020, 186: 113308.
[13] ZHANG H Z, SUN N, QIN F, et al. Structure analysis of components in polymyxin E sulfate by high performance liquid chromatography-quadrupole/time of flight mass spectrometry. China Pharm J (中国药学杂志), 2021, 56(1): 54-62.
[14] ZHANG H Z, SUN N, LUO W Y, et al. Structure elucidation of new kinds of bacitracin sulfonic acid based on high performance liquid chromatography-quadrupole/time of flight-tandem mass spectrometry. Int J Mass Spectrom, 2021, 461: 116499.
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脚注
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基金
上海市2020年度“科技创新行动计划”科学仪器领域项目资助(20142202200);上海市药品监督管理局课题资助(YB-2020-04)
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