Characterization of 12 Unknown Photodegradation Impurities of Tunlametinib Capsules Using Liquid Chromatography Coupled With ion Trap/Time-Of-Flight Mass Spectrometry

IF 1.7 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS

Rapid Communications in Mass Spectrometry Pub Date : 2025-07-28 DOI:10.1002/rcm.10113

Ying Yang, Jiarui Gao, Hongxia Zeng

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引用次数: 0

Abstract

Rationale

In March 2024, tunlametinib capsules, a Class 1 new drug (referring to active pharmaceutical ingredients and formulations not previously marketed either nationally or globally), were approved in China for treating patients with advanced melanoma and neuroblastoma RAS viral oncogene homologue mutations who experienced disease progression or intolerance to anti-PD-1/PD-L1 therapy. Risk assessment of impurity profiles is essential for drug safety and efficacy in clinical applications. This study characterized impurity profiles in tunlametinib capsules induced by photodegradation.

Methods

Initial high-performance liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (HPLC/IT-TOF MS) in positive ion mode was first performed to determine the m/z values of protonated ions and predict the formulas of the detected impurities. Subsequent LC-MSⁿ analyses (n = 2–4) of target compounds elucidated comprehensive structural features.

Results

Twelve previously unidentified photodegradation impurities in tunlametinib capsules were characterized using HPLC/IT-TOF MS.

Conclusions

Structural elucidation of 12 previously uncharacterized photodegradation impurities was achieved through HPLC/IT-TOF MS. These findings establish a scientific foundation for refining quality specifications of tunlametinib.

Abstract Image

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液相色谱-离子阱/飞行时间质谱联用表征Tunlametinib胶囊中12种未知光降解杂质

2024年3月，一类新药tunlametinib胶囊（指以前未在国内或全球上市的活性药物成分和制剂）在中国被批准用于治疗晚期黑色素瘤和神经母细胞瘤RAS病毒癌基因同源突变患者，这些患者经历了疾病进展或对抗pd -1/PD-L1治疗不耐受。在临床应用中，杂质谱的风险评估对药物的安全性和有效性至关重要。本研究表征了光降解诱导的图拉美替尼胶囊的杂质谱。方法采用高效液相色谱联用离子阱/飞行时间质谱法（HPLC/IT-TOF MS），测定质子化离子的m/z值，并预测杂质的组成。随后的LC-MSn分析（n = 2-4）阐明了目标化合物的综合结构特征。结果采用HPLC/IT-TOF质谱法对图拉美替尼胶囊中12种未鉴别的光降解杂质进行了表征。结论采用HPLC/IT-TOF质谱法对12种未鉴别的光降解杂质进行了结构解析，为完善图拉美替尼的质量标准奠定了科学基础。

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来源期刊

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.