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目的应用在线脱盐-高效液相色谱-离子阱-飞行时间质谱(2D-LC-IT-TOF/MS)法鉴定盐酸多西环素片在药典条件下检出的有关物质结构,并推断盐酸多西环素在溶液状态下的降解途径。方法 LC 1 stD色谱条件:InertSustain~(TM)C_(18)(4.6 mm×150 mm,5μm)色谱柱,醋酸盐缓冲液[0.25 mol·L~(-1)醋酸-0.1 mol·L~(-1)EDTA钠盐-三乙胺(100:10:1),用醋酸或氨水调节pH值至8.8]-乙腈(85:15)为流动相进行等度洗脱;LC 2ndD色谱条件:InertSustain~(TM)C_(18)(2.1 mm×50 mm,2μm)色谱柱,0.1%甲酸冰溶液为流动相A,0.1%甲酸福乙睛为流动相B,进行梯度洗脱;质谱条件:ESI正负离子同时检测,雾化气流速1.5L·min~(-1),干燥气流速10 L·min~(-1)脱溶剂管温度200℃。根据多级质谱信息来推定药典条件下检出的有关物质结构和强制降解溶液中产生的杂质结构。结果在盐酸多西环素片中共检出8个有关物质推定出其中4个含量大于0.1%的有关物质的结构,分别为4-表多西环素、美他环素、β-多西环素、2-乙酰-6-脱碳酰胺多西环素。盐酸多西环素溶液在碱性条件下易降解,生成脱酮基开环物;在高温条件下容易产生4-表多西环素,并伴有少量4-表-6-表多西环素的生成;在酸性条件和光照条件下相对稳定。结论建立的方法可用于盐酸多西环素中杂质的鉴定,为盐酸多西环素的质量控制与工艺优化研究提供可靠的分析手段。
OBJECTIVE To identify the related substance structure of doxycycline hyclate under the condition of Pharmacopoeia by on-line desalting-high performance liquid chromatography-ion trap-time of flight mass spectrometry (2D-LC-IT-TOF / MS) The degradation of ciclinoid in solution. Method LC 1 stD Chromatographic conditions: InertSustain ™ C 18 (4.6 mm × 150 mm, 5 μm) column, acetate buffer [0.25 mol·L -1 acetic acid-0.1 mol·L -1 (-1) EDTA sodium salt-triethylamine (100: 10: 1), using acetic acid or ammonia to adjust the pH to 8.8] -acetonitrile (85:15) as the mobile phase; LC 2ndD chromatographic conditions: InertSustain ~ (TM) C 18 (2.1 mm × 50 mm, 2 μm) column, 0.1% formic acid ice solution as mobile phase A, 0.1% formic acid asoride as mobile phase B, gradient elution; The positive and negative ions of ESI were detected simultaneously. The atomization gas flow rate was 1.5L · min ~ (-1) and the drying gas flow rate was 10L · min ~ (-1). The desolvation tube temperature was 200 ℃. Based on the multi-stage MS information, the structure of the substance detected in the Pharmacopoeia and the structure of the impurity generated in the forcibly degraded solution are estimated. Results In the doxycycline hyclate, eight related substances were found, of which four were more than 0.1%. The structures of the related substances were as follows: 4-epicatenin, mesotrione, β-docetaxel 2-acetyl-6-deoxyamide doxycycline. The doxycycline hydrochloride solution is easily degraded under alkaline conditions to form a de-ketocyclic ring-opening product; 4-epidophycin is easily produced under high temperature with a small amount of 4-epi-6- The formation of prime; Under acidic conditions and light conditions are relatively stable. Conclusion The established method can be used to identify the impurities in doxycycline hydrochloride and provide a reliable analytical method for the quality control and process optimization of doxycycline hydrochloride.