度洛西汀杂质13 | 199191-67-8

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 度洛西汀杂质13
• 英文名称: duloxetine phthalamide
• 英文别名: (S)-Duloxetine Phthalamide；2-[methyl-[(3S)-3-naphthalen-1-yloxy-3-thiophen-2-ylpropyl]carbamoyl]benzoic acid
• CAS: 199191-67-8
• 化学式: C₂₆H₂₃NO₄S
• 分子量: 445.539
• InChiKey: QYWSULHSCQVWPV-QHCPKHFHSA-N

物化性质

• 熔点：
  >183°C (dec.)
• 沸点：
  695.1±55.0 °C(Predicted)
• 密度：
  1.296±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  95.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苯酐 、 盐酸度洛西汀 在 三乙胺 作用下， 以 氯仿 为溶剂， 反应 0.25h， 生成 度洛西汀杂质13
  参考文献：
  名称：

  Characterization of Impurities Formed by Interaction of Duloxetine HCl with Enteric Polymers Hydroxypropyl Methylcellulose Acetate Succinate and Hydroxypropyl Methylcellulose Phthalate

  摘要：

  Duloxetine hydrochloride ((S)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine hydrochloride) has been found to react with polymer degradation products or residual free acids present in the enteric polymers hydroxypropyl methylcellulose acetate succinate (HPMCAS) and hydroxypropyl methylcellulose phthalate (HPMCP) in dosage formulations to form succinamide and phthalamide impurities, respectively. The rate of formation of the impurities is accelerated by heat and humidity. The structures were deduced using molecular weights obtained from LC-MS experiments and confirmed by comparison of UV spectra, HPLC retention times, and electrospray mass spectra to independently synthesized material. It is proposed that polymer-bound succinic and phthalic substituents can be cleaved from the polymer, resulting in the formation of either the free acids or the anhydride. It is postulated that the reaction is enabled by migration of either (1) the free acid or anhydride or (2) the parent drug through the formulation. The formation of these impurities was minimized by increasing the thickness of the physical barrier separating the enteric coating from the drug.

  DOI：

  10.1021/js970133r

文献信息

• Characterization of Impurities Formed by Interaction of Duloxetine HCl with Enteric Polymers Hydroxypropyl Methylcellulose Acetate Succinate and Hydroxypropyl Methylcellulose Phthalate
  作者：Patrick J. Jansen、Peter L. Oren、Craig A. Kemp、Steven R. Maple、Steven W. Baertschi

  DOI：10.1021/js970133r

  日期：1998.1

  Duloxetine hydrochloride ((S)-N-methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamine hydrochloride) has been found to react with polymer degradation products or residual free acids present in the enteric polymers hydroxypropyl methylcellulose acetate succinate (HPMCAS) and hydroxypropyl methylcellulose phthalate (HPMCP) in dosage formulations to form succinamide and phthalamide impurities, respectively. The rate of formation of the impurities is accelerated by heat and humidity. The structures were deduced using molecular weights obtained from LC-MS experiments and confirmed by comparison of UV spectra, HPLC retention times, and electrospray mass spectra to independently synthesized material. It is proposed that polymer-bound succinic and phthalic substituents can be cleaved from the polymer, resulting in the formation of either the free acids or the anhydride. It is postulated that the reaction is enabled by migration of either (1) the free acid or anhydride or (2) the parent drug through the formulation. The formation of these impurities was minimized by increasing the thickness of the physical barrier separating the enteric coating from the drug.