中国新药杂志

LC-MS法测定塞来昔布中2个苯肼类基因毒性杂质

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冯蕊 ¹^,² , 陈冠军 ²^,³ , 刘莉 ²^,³ , 汪生 ²^,³

中国新药杂志 | 实验研究 2021,30(2): 182-186

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中国新药杂志 |实验研究 2021 , 30 (2) : 182 -186

LC-MS法测定塞来昔布中2个苯肼类基因毒性杂质

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冯蕊¹^,², 陈冠军²^,³, 刘莉²^,³, 汪生²^,³

作者信息

¹安徽医科大学　药学院，合肥　230032

²安徽医科大学　重大自身免疫性疾病安徽省重点实验室，合肥　230032

³安徽医科大学　科研实验中心，合肥　230032

通讯作者:

汪生，男，助理实验师，主要从事质谱相关研究工作。联系电话：（0551）65160310，E-mail：wangsheng_cpu@163.com。

作者简介:

冯蕊，女，助理实验师，主要从事药学相关研究工作。联系电话：（0551）65161217，E-mail：fengruicpu@126.com。

Determination of two phenylhydrazine-like genotoxic impurities in celecoxib by LC-MS

Rui FENG¹^,², Guan-jun CHEN²^,³, Li LIU²^,³, Sheng WANG²^,³

Affiliations

¹Anhui Medical University School of Pharmacy, Hefei 230032, China

²Anhui Medical University Anhui Province Key Laboratory of Major Autoimmune Diseases, Hefei 230032, China

³Anhui Medical University the Center for Scientific Research of Anhui Medical University, Hefei 230032, China

出版时间: 2021-01-30

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摘要

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目的：

建立液相色谱-质谱（LC-MS）法测定塞来昔布中对肼基苯磺酰胺（SHH）和对甲苯腙基苯磺酰胺（MAP）2个苯肼类基因毒性杂质。

方法：

采用Thermo BDS Hypersil C₁₈（100 mm×4.6 mm，2.4 μm）色谱柱，以0.1%甲酸铵-0.1%甲酸水溶液∶甲醇（90∶10）溶液为流动相A，以甲醇为流动相B进行线性梯度洗脱。样品中加入5%二巯基苏糖醇的醋酸铵缓冲液作为稳定剂，在质谱电喷雾正离子化多反应监测模式下，以内标法进行定量测定。

结果：

SHH和MAP在20~200 ng·mL^-1浓度范围内线性关系良好；平均回收率分别为99.7%（RSD=6.0%，n=9）和97.6%（RSD=5.1%，n=9）。检测限为10 ng·mL^-1，定量限为20 ng·mL^-1，对照溶液和供试品溶液于4 ℃进样盘放置4 h内稳定。

结论：

本实验建立的LC-MS测定法适用于塞来昔布中SHH和MAP 2个苯肼类基因毒性杂质的检测。

关键词

塞来昔布 / 对肼基苯磺酰胺 / 对甲苯腙基苯磺酰胺 / 基因毒性杂质 / 液质联用 / 限度检查

Abstract

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Objective:

To establish an LC-MS method for the determination of two phenylhydrazine-like genotoxic impurities [(4-sulfamoylphenyl) hydrazine, SHH; (4-methyl-acetophenone) para-sulfonamide phenylhydrazine, MAP] in celecoxib.

Methods:

The separation was established on Thermo BDS Hypersil C₁₈(100 mm×4.6 mm, 2.4 μm) column by liner gradient elution using (0.1% ammonium formate-0.1% formic acid buffer solution)-methanol 90∶10 as mobile phase A and methanol as mobile phase B. 5 mmol·L^-1 dithiothreitol buffer solution was used as the antioxidant, the determination was carried out by multiple reactions monitoring mode with positive electrospray ionization, meanwhile, the analytes were quantitatively determined by internal reference method.

Results:

The established LC-MS method displayed satisfactory linearity over the concentration range of 20~200 ng·mL^-1. The average recovery was 99.7% (RSD=6.0%) for SHH and 97.6% (RSD=5.1%) for MAP. The limit of detection and limit of quantification were 10 ng·mL^-1 and 20 ng·mL^-1, respectively. The reference and test solutions were stable at 4 ℃ for 4 h.

Conclusion:

The established LC-MS method is suitable for simultaneous determination of SHH and MAP genotoxic impurities in celecoxib.

Key words

celecoxib / (4-sulfamoylphenyl) hydrazine / (4-methyl-acetophenone) para-sulfonamide phenylhydrazine / genotoxic impurity / LC-MS / quantification

引用本文

冯蕊, 陈冠军, 刘莉, 汪生. LC-MS法测定塞来昔布中2个苯肼类基因毒性杂质. 中国新药杂志, 2021 , 30 (2) : 182 -186 .

Rui FENG, Guan-jun CHEN, Li LIU, Sheng WANG. Determination of two phenylhydrazine-like genotoxic impurities in celecoxib by LC-MS[J]. Chinese Journal of New Drugs, 2021 , 30 (2) : 182 -186 .

参考文献

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2021年第30卷第2期

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首发时间：2026-10-29
出版时间：2021-01-30

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录用日期：2020-05-31

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¹安徽医科大学　药学院，合肥　230032

²安徽医科大学　重大自身免疫性疾病安徽省重点实验室，合肥　230032

³安徽医科大学　科研实验中心，合肥　230032

通讯作者:

汪生，男，助理实验师，主要从事质谱相关研究工作。联系电话：（0551）65160310，E-mail：wangsheng_cpu@163.com。

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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