酒石酸唑吡坦片中杂质的色谱-质谱结构鉴定

目的：采用LC-MS对酒石酸唑吡坦片中的杂质进行结构鉴定。方法：通过酸、碱、高温、氧化和光照对酒石酸唑吡坦片中的杂质进行富集，采用液相色谱-超高分辨飞行时间质谱对未知杂质进行鉴定，色谱柱为C₁₈（2.1 mm×100 mm，1.9 μm），流动相为10 mmol·L^-1乙酸铵溶液-甲醇-乙腈（53∶23∶18），采用ESI正离子模式进行质谱扫描。结果：结合酒石酸唑吡坦的处方工艺初步推测了6个杂质的化学结构。杂质1：4-（二甲胺基）-3-（6-甲基-2-对甲苯基咪唑并［1，2-a］吡啶-3-基）-4-氧代丁酸；杂质4：N-甲基-2-（6-甲基-2-对甲苯基咪唑并［1，2-a］吡啶-3-基）乙酰胺；杂质5：2-羟基-N，N-二甲基-2-（6-甲基-2-对甲苯基咪唑并［1，2-a］吡啶-3-基）乙酰胺；杂质6：N，N-二甲基-2-（6-甲基-2-对甲苯基咪唑并［1，2-a］吡啶-3-基）-2-氧代乙酰胺；杂质7：N，N-二甲基-2-（6-甲基-2-对甲苯基-2，3-二氢咪唑并［1，2-a］吡啶-3-基）乙酰胺；杂质8：6-甲基-2-对甲苯基咪唑并［1，2-a］吡啶-3-甲醛。它们都具有6-甲基-2-苯基咪唑并［1，2-a］吡啶的母核。结论：超高分辨飞行时间质谱技术能够有效地用于药物中杂质的鉴定，酒石酸唑吡坦杂质研究可为其质量控制和工艺优化提供参考依据。

Objective: To separate and identify the impurities in zolpidem tartrate tablets by a LC-MS method.Methods: Target impurities were produced under stress conditions including acid, base, high temperature, oxidation and light in zolpidem tartrate tablets.A LC-UHR-TOF/MS method was established by using C₁₈(2.1 mm×100 mm, 1.9 μm)column with 10 mmol·L^-1 ammonium acetate solution-methanol-acetonitrile(53:23:18)as the mobile phase.ESI source was adopted.Results: The structures of six impurities were tentatively deduced by using LC-MS with positive ion mode referred to the formulation study.Impurity 1:4-(dimethylamino)-3-(6-methyl-2-(p-tolyl) imidazo[1, 2-a]pyridin-3-yl)-4-oxobutanoic acid; impurity 4:N-methyl-2-(6-methyl-2-(p-tolyl)imidazo[1, 2-a]pyridin-3-yl)acetamide; impurity 5:2-hydroxy-N, N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1, 2-a]pyridin-3-yl)acetamide; impurity 6:N, N-dimethyl-2-(6-methyl-2-(p-tolyl)imidazo[1, 2-a] pyridin-3-yl)-2-oxoacetamide; impurity 7:N, N-dimethyl-2-(6-methyl-2-(p-tolyl)-2, 3-dihydroimidazo[1, 2-a]pyridin-3-yl)acetamide; impurity 8:6-methyl-2-(p-tolyl)imidazo[1, 2-a]pyridine-3-carbaldehyde.Each of six impurities had the same nuclear parent(6-methyl-2-phenyl-2, 3-dihydroimidazo[1, 2-a]pyridin).Conclusion: LC-MS method is useful for the investigation and structure identification of impurities in pharmaceuticals.The impurities observed in zolpidem tartrate may provide valuable support for manufacturing process improvement and quality control.

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