Impurity profiling of Compound Amino Acid Injection (6AA) using ion-pair high performance liquid chromatography coupled with corona-charged aerosol detection and high resolution mass spectrometry
| Autor: | Limin Zuo, Xuejia Zhao, Guangzhi Shan, Xiaodan Qiu, Zhiling Zhu, Ting Zhao, Zhong-Hao Sun, Shengnan Sun, Shijie Xu, Jing Yao |
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| Rok vydání: | 2021 |
| Předmět: |
Clinical Biochemistry
Pharmaceutical Science Mass spectrometry Orbitrap 01 natural sciences High-performance liquid chromatography Mass Spectrometry Analytical Chemistry law.invention chemistry.chemical_compound law Impurity Drug Discovery Trifluoroacetic acid Amino Acids Chromatography High Pressure Liquid Spectroscopy Aerosols Detection limit Chromatography 010405 organic chemistry 010401 analytical chemistry Heptafluorobutyric acid 0104 chemical sciences chemistry Linear range Drug Contamination |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 201:114099 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2021.114099 |
| Popis: | The complex industrial production process of amino acids (AAs) leads to the existence of a certain amount of impurities in Compound Amino Acid Injection (6AA). It is difficult to obtain its comprehensive and systematic impurity profile using conventional ultraviolet (UV) detectors due to lack of a suitable chromophore in the structures of AAs and their impurities. In our study, a universal ion-pair high performance liquid chromatography (HPLC) method combined with high resolution mass spectrometer (HRMS) and charged aerosol detection (CAD) was developed to identify and determine the content of impurities in Compound Amino Acid Injection (6AA), respectively. After optimizing the content of trifluoroacetic acid (TFA) and heptafluorobutyric acid (HFBA) in the mobile phase on a C18 AQ column, HPLC-CAD method was developed and nine unknown impurities were detected. These impurities were successfully identified using HPLC coupled with orbitrap mass spectrometry and confirmed with their reference substances. The CAD parameters setting was optimized to improve the sensitivity and linearity of the methods before the developed method was validated. The results of validation reflected that the limit of detection (LOD) was approximately 2 ng (corresponding to approximately 0.02 % of L-isoleucine in injection). Under the optimized power function value (PFV) of CAD, the linear range of each impurity was 1 ∼ 200 μg mL-1 (the linear range of one of the impurities with higher content was 2 ∼ 400 μg mL-1) with coefficients of determination (R2) greater than 0.998. The recovery rates for nine impurities were 93.37 % ∼ 110.23 %. This study made full use of the qualitative functions of HRMS and the versatility of CAD, revealing possible impurities in the 6AA injection, which could provide reference for the safety research of it. |
| Databáze: | OpenAIRE |
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