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目的:采用LC-MS技术对盐酸左西替利嗪片中有关物质进行结构鉴定。方法:采用Welch Xtimate C18色谱柱(250 mm×4.6 mm,5μm),以甲醇-四氢呋喃-磷酸盐溶液(磷酸二氢钠3.1 g,用水溶解稀释至1 000 mL,用磷酸调节pH至2.9)(44.5∶5.5∶50)为流动相等度洗脱,对盐酸左西替利嗪片中有关物质进行分离;应用Kinetex C18(100 mm×n2.1 mm,1.7μm)色谱柱,以水(含0.05%甲酸)-甲醇(含0.05%甲酸)流动相梯度洗脱,采用色谱-质谱(MS)技术测定离子准确质量并分析离子特征,结合对照品确证有关物质结构;结合处方分析,推测未知杂质结构,并揭示杂质产生的来源。结果:在所建立的条件下,盐酸左西替利嗪与其有关物质分离良好,检测出10个有关物质,并综合分析、鉴定了有关物质结构,推测其中最大的未知杂质为左西替利嗪与残留乙醇酯化生成的2-[2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乙酯,另2个较大未知杂质为是左西替利嗪的羧基与乳糖不同位置的羟基产生的酯化产物(R)-2-[2-[4-[(4-氯苯基)(苯基)甲基]哌嗪-1-基]乙氧基]乙酸乳糖酯。结论:本研究为盐酸左西替利嗪片的处方研究及制剂工艺提供指导。
OBJECTIVE: To identify the related substances in levocetirizine hydrochloride tablets by LC-MS. Methods: The samples were separated on a Welch Xtimate C18 column (250 mm × 4.6 mm, 5 μm) with a methanol-tetrahydrofuran-phosphate solution (3.1 g of sodium dihydrogen phosphate, diluted to 1000 mL with water and adjusted to pH 2.9 with phosphoric acid) 44.5: 5.5: 50) was used as mobile phase to elute the levocetirizine hydrochloride tablets. The separation was carried out using Kinetex C18 (100 mm × n2.1 mm, 1.7 μm) % Formic acid) -methanol (containing 0.05% formic acid). The exact mass of the ion was determined by chromatographic-mass spectrometry (MS) and the ion characteristics were analyzed. The structure of the substance was confirmed with the reference substance. , And reveals the source of impurities. Results: Under the established conditions, levocetirizine hydrochloride and its related substances were well separated and 10 related substances were detected. Based on the comprehensive analysis and identification of the related substances, it was speculated that the largest unknown impurity was levocetirizine Ethyl 2- [2- [4- [(4-chlorophenyl) (phenyl) methyl] piperazin-1-yl] ethoxy] acetate esterified with residual ethanol and the other two larger An unknown impurity is an esterification product of a hydroxyl group at a different position of a carboxyl group and a lactose of levocetirizine (R) -2- [2- [4- [(4-chlorophenyl) (phenyl) methyl] Oxazin-1-yl] ethoxy] lactose. Conclusion: This study provides a guideline for the formulation and preparation of levocetirizine hydrochloride tablets.