Determination of Potential Genetoxic Impurity in Ledipasvir by UPLC-MS/MS
- VernacularTitle:UPLC-MS/MS法检测雷迪帕韦原料药中潜在基因毒性杂质残留量
- Author:
Chunling LIU
;
Chunju LIU
;
Xi LIU
;
Yujie CHEN
;
Zhihuai LI
;
Yanhua XI
- Keywords:
Ledipasvir;
1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide;
Potential genetoxic impurity;
UPLC-MS/MS
- From:
China Pharmacist
2017;20(6):1139-1141
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To establish a UPLC-MS/MS method for the determination of the residual quantity of potential genetoxic impurity 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) in ledipasvir.Methods: The chromatographic conditions were as follows: an Agilent ZORBAX SB-C18 (75 mm×4.6 mm, 3.5 μm) column was used with methanol-0.1% formic acid (50∶50) as the mobile phase.The flow rate was 0.3 ml·min-1.The column temperature was 30 ℃ and the injection volume was 5 μl.The mass spectrometry conditions were as follows: electrospray ionization source (ESI), multistage reaction monitoring (MRM), positive ion scanning mode, ion spray voltage of 2 500 V, ion source temperature of 500 ℃, atomization gas of 379.0 kPa, auxiliary gas of 275.6 kPa, curtain gas of 137.8 kPa, collision gas of 41.3 kPa, ion collision energy of 15 V and scan time of 100 ms.The MRM ion pair for quantitative analysis was m/z→156.2/86.1.Results: The linear range of EDC was 0.03-2.25 μg·ml-1 (r=0.999 0).The limit of detection was 0.03 ng and the limit of quantitation was 0.08 ng.The average recovery was 98.3%(RSD=5.7%, n=9).Conclusion: The method is simple, rapid and accurate, and can be used for the quality control of EDC in ledipasvir.
