Study on the structure of an unknown impurity in carboplatin injection and the relationship with the excipient
10.16438/j.0513-4870.2017-1126
- VernacularTitle:卡铂注射液未知杂质结构及其与辅料的相关性研究
- Author:
Wei JIN
1
;
Wen-ming JIANG
1
;
Qian LIU
1
;
Xuan GAO
1
;
Ye ZHANG
1
;
Dan GUO
1
;
Min QIAN
1
;
Mei-ting REN
1
;
Yong-jian YANG
1
Author Information
1. Shanghai Institute for Food and Drug Control, Shanghai 201203, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
carboplatin injection;
impurity containing platin;
disodium edentate;
1,1-cyclobutanedicarboxylic acid;
2D-LC-MS-QTOF
- From:
Acta Pharmaceutica Sinica
2018;53(4):604-608
- CountryChina
- Language:Chinese
-
Abstract:
The study was designed to establish a 2D UPLC-QTOF method to extrapolate the structure of an unknown substance in carboplatin injection and its relationship with the excipient. By using phenyl-hexyl column (250 mm×4.6 mm, 5 μm) with mobile phase consisting of tetrabutylammonium sulfate buffer (pH 7.5) and acetonitrile in gradient elution mode, an unknown impurity in carboplatin injection was found and quantitatively determined. Then a 2D UPLC-QTOF, HSS T3 column (100 mm×2.1 mm, 1.7 μm) was employed to confirm the molecular weight and the structure of the unknown impurity (electrospray ionization source, positive ion mode, MSE mode) with mobile phase consisting of 0.1% formic acid and acetonitrile. The relationship among impurities, API and excipient was investigated by accelerated stability test with ICP-MS/MS, ICP-AES. Results showed that disodium edetate in the formulation interacted with carboplatin producing an unknown impurity containing platin, and induced the increase of 1,1-cyclobutanedicarboxylic acid. The research should be done on the rationality of the addition of disodium edetate in such injections containing heavy metals.
