棕榈酸曲安奈德中未知杂质的鉴定

doi:10.5246/jcps.2022.04.024

中国药学(英文版) ›› 2022, Vol. 31 ›› Issue (4): 270-278.DOI: 10.5246/jcps.2022.04.024

棕榈酸曲安奈德中未知杂质的鉴定

金祥飞¹, 程闽玥¹, 钟斯卉¹, 徐云根², 沈卫阳¹^,³^,^*()

1. 中国药科大学理学院分析化学教研室, 江苏南京 211198
2. 中国药科大学药物化学系, 江苏省药物设计与优化重点实验室, 江苏南京 211198
3. 药物质量与安全预警教育部重点实验室, 江苏南京 210009

收稿日期:2021-11-25 修回日期:2021-12-08 接受日期:2021-12-15 出版日期:2022-04-30 发布日期:2022-04-30
通讯作者: 沈卫阳
作者简介:
+ Tel.: +86-18061297399, E-mail: shenweiyang@cpu.edu.cn

Identification of unknown impurities in triamcinolone acetonide palmitate

Xiangfei Jin¹, Minyue Cheng¹, Sihui Zhong¹, Yungen Xu², Weiyang Shen¹^,³^,^*()

1 Department of Analytical Chemistry, China Pharmaceutical University, Nanjing 211198, China
2 Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China
3 Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009, China

Received:2021-11-25 Revised:2021-12-08 Accepted:2021-12-15 Online:2022-04-30 Published:2022-04-30
Contact: Weiyang Shen

摘要/Abstract

摘要：

利用HPLC-DAD和HPLC-MS联用技术对棕榈酸曲安奈德中含量超过0.1%的未知杂质进行结构分析, 合成杂质后通过柱色谱法进行纯化。根据NMR、IR和MS的结果, 确定这两种杂质分别为9-氟-11β,21-二羟基-16α,17-异丙基双氧孕甾-1,4 -二烯- 3,20 -二酮21-肉豆蔻酸酯和硬脂酸酯。

关键词: 棕榈酸曲安奈德, 杂质鉴定, HPLC-DAD, LC-MS

Abstract:

In the present study, we analyzed the structures of the two unknown impurities that were contained more than 0.1% in triamcinolone acetonide palmitate by using HPLC-DAD and HPLC-MS hyphenated techniques, and these impurities were synthesized and purified by column chromatography. Based on the results of NMR spectroscopy, IR spectroscopy, and MS, the two impurities were confirmed as 9-fluoro-11β,21-dihydroxy-16α,17-(isopropylidenedioxy)pregna-1,4-diene-3,20-dione 21-myristate and stearate, respectively.

Key words: Triamcinolone acetonide palmitate, Impurity identification, HPLC-DAD, LC-MS

Supporting:

金祥飞, 程闽玥, 钟斯卉, 徐云根, 沈卫阳. 棕榈酸曲安奈德中未知杂质的鉴定[J]. 中国药学(英文版), 2022, 31(4): 270-278.

Xiangfei Jin, Minyue Cheng, Sihui Zhong, Yungen Xu, Weiyang Shen. Identification of unknown impurities in triamcinolone acetonide palmitate[J]. Journal of Chinese Pharmaceutical Sciences, 2022, 31(4): 270-278.

图/表 10

Figure 1. Chromatogram of the related substances of triamcinolone acetonide palmitate.

Table 1. Results of related substances of triamcinolone acetonide palmitate.

Figure 2. Mass spectra of triamcinolone acetonide palmitate, impurity c and h. (a) Triamcinolone acetonide palmitate; (b) impurity c; (c) impurity h.

Figure 3. Synthesis of triamcinolone acetonide myristate and triamcinolone acetonide stearate.

Figure 4. Chromatograms of triamcinolone acetonide palmitate, triamcinolone acetonide myristate, and triamcinolone acetonide stearate.

Table 2. Results of IR spectra of triamcinolone acetonide myristate and triamcinolone acetonide stearate.

Figure 5. Proposed mass fragmentation pathway of protonated triamcinolone acetonide myristate.

Figure 6. Proposed mass fragmentation pathway of protonated triamcinolone acetonide stearate.

Figure 7. The chemical structures of triamcinolone acetonide myristate and triamcinolone acetonide stearate. (a) Triamcinolone acetonide myristate; (b) triamcinolone acetonide stearate.

Table 3. Results of 1H NMR spectra of triamcinolone acetonide myristate and triamcinolone acetonide stearate.

[1]	The United States Pharmacopeial Convention. Triamcinolone Acetonide, USP40–NF35. Rockville, MD. 2015, 6558–6559.
[2]	The United States Pharmacopeial Convention. Cetyl Palmitate, USP40–NF35. Rockville, MD. 2015, 7599–7600.
[3]	International Conference on Harmonisation. Impurities in New Drug Substances Q3A(R2). 2006.
[4]	International Conference on Harmonisation. Impurities in New Drug Products Q3B(R2). 2006.
[5]	Krstulovic, A.M.; Lee, C.R.; Firmin, S.; Jacquet, G.; Tessier, D. Applications of LC-MS methodology: in the development of pharmaceuticals. LC GC Eur. 2002, 15, 31–41.

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棕榈酸曲安奈德中未知杂质的鉴定

Identification of unknown impurities in triamcinolone acetonide palmitate

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