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中国药物评价 ›› 2021, Vol. 38 ›› Issue (1): 52-58.

• 评价技术与方法 • 上一篇    下一篇

UPLC法测定度鲁特韦有关物质含量

孙宝丹1,2, 应俊1, 王忠美2, 左莉2   

  1. 1. 宁波诺柏医药有限公司, 浙江 宁波 315000;
    2. 浙江朗华制药有限公司, 浙江 台州 317000
  • 收稿日期:2020-11-30 修回日期:2021-02-04 出版日期:2021-02-28 发布日期:2021-02-28

Determination the Assay of Related Substances in Dolutegravir by UPLC

  1. 1. Ningbo Nuobai Pharmaceutical Co., Ltd, Zhejiang Ningbo 315000, China;
    2. Zhejiang Langhua Pharmaceutical CO.,TLD, Zhejiang Taizhou 317000, China
  • Received:2020-11-30 Revised:2021-02-04 Online:2021-02-28 Published:2021-02-28

摘要: 目的:建立测定度鲁特韦原料药有关物质含量的超高效液相色谱方法。方法:色谱柱为Waters BEH C18(2.1 mm×150 mm×1.7 μm),流动相:10 mmol·L-1甲酸铵溶液(pH=2.5)为流动相A,乙腈为流动相B,梯度洗脱:0~15 min,流动相B 20%~80%,柱温30 ℃,流速0.28 mL·min-1,进样量1.0 μL,检测波长246 nm。结果:度鲁特韦与各杂质之间的分离度均>1.5;杂质A~D的检测限和定量限分别为8 ng·mL-1和25 ng·mL-1;度鲁特韦浓度和杂质A~D浓度在相应浓度范围内与峰面积线性关系良好,相关系数r均>0.998;杂质A~D加样回收率均在80.0%~120.0%之间,RSD<5.0% (n=9),度鲁特韦含量准确度结果在99.0%~101.0%范围内,RSD<0.2% (n=9),3批原料药含量结果分别为99.79%,99.77%,100.03%,杂质A分别为0.10%,0.10%,0.11%,杂质B、C均未检出,未知单杂均小于0.05%,总杂分别为0.15%,0.13%,0.14%。结论:本研究建立的UPLC法,专属性强,重复性好,灵敏度和准确度高,可作为度鲁特韦原料药有关物质和含量的控制方法。
   

关键词: font-size:medium, ">超高效液相色谱;有关物质;含量;度鲁特韦;测定

Abstract: Objective: To establish UPLC method for determination of related substances and assay in Dolutegravir drug substance. Methods: The determination was carried out on Waters BEH C18 (2.1 mm×150 mm×1.7 μm) with 10 mmol·L-1 ammonium formate buffer pH=2.5 adjusted with formic acid(mobile phase A) and acetonitrile(mobile phase B) as mobile phase. Linearity gradient elution was run by mobile phase B changed from 20% to 80% in the range of 0~15 min, with the column temperature of 30 ℃, and the injection volume of 1.0 uL at the flow rate of 0.28 mL(min, monitored at 246 nm. Results: The resolutions between Dolutegravir peak and other impurities peaks were not less than 1.5. The LOD and LOQ for impurity A, B, C and D all were 8 ng·mL-1 and 25 ng·mL-1, respectively. The calibration curves for Dolutegravir and Impurity A, B, C and D were all linear in the range of the corresponding concentration of them with r>0.998. The recovery of Impurity A, B, C and D all were within the range 80%~120%, and RSD were less than 5.0%(n=9). The accuracy results of Dolutegravir was within the range of 99.0%~101.0%, and RSD was not more than 0.2%(n=9). The assay results of 3 batches of Dolutegravir drug substance were 99.79%, 99.77% and 100.03% respectively, and the content of Impurity A were 0.10%, 0.10% and 0.11% respectively. Impurity B and C were both no detection, the results of unknown impurity all were less than 0.05%, and the results of total impurities were 0.15%, 0.13% and 0.14% respectively. Conclusion: The UPLC method is specific, repeatable, sensitive and accurate, and is effective for quality control in Dolutegravir. 
 

Key words: font-size:medium, ">UPLC; Related substance; Assay; Dolutegravir; Determination

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