Determination of Isobutyl Chloroformate Residue in Agatroban by Derivatization-Gas Chromatography-Mass Spectrometry
10.19756/j.issn.0253-3820.221579
- VernacularTitle:衍生化-气相色谱-质谱法检测阿加曲班中氯甲酸异丁酯残留
- Author:
Chong QIAN
1
,
2
;
Bo-Kai MA
;
Chuang NIU
;
Shan-Shan LIU
;
Wen-Wen HUANG
;
Xin-Lei GOU
;
Wei WANG
;
Mei ZHANG
;
Xue-Li CAO
Author Information
1. 北京工商大学轻工科学与工程学院,北京食品营养与人类健康高精尖创新中心,北京 100048
2. 北京市科学技术研究院分析测试研究所(北京市理化分析测试中心),有机材料检测技术与质量评价北京市重点实验室,北京 100094
- Keywords:
Agatroban;
Isobutyl chloroformate;
Derivatization reaction;
Gas chromatography-mass spectrometry;
Methyl isobutyl carbonate
- From:
Chinese Journal of Analytical Chemistry
2024;52(1):113-120
- CountryChina
- Language:Chinese
-
Abstract:
A derivatizaton method combined with gas chromatography-mass spectrometry(GC-MS)was established for detection of isobutyl chloroformate(IBCF)residue in active pharmaceutical ingredient of agatroban.The extraction and derivatization reagents,derivatization time,qualitative and quantitative ions were selected and optimized,respectively.The possible mechanism of derivatization and characteristic fragment ions fragmentation were speculated.The agatroban samples were dissolved and extracted by methanol,and the residual IBCF was derived with methanol to generate methyl isobutyl carbonate(MIBCB).After 24 h static derivatization at room temperature,IBCF was completely transformed into MIBCB,which could be used to indirectly detect IBCF accurately.The results showed that the linearity of this method was good in the range of 25-500 ng/mL(R2=0.9999).The limit of detection(LOD,S/N=3)was 0.75 μg/g,and the limit of quantification(LOQ,S/N=10)was 2.50 μg/g.Good recoveries(95.2%-97.8%)and relative standard deviations(RSDs)less than 3.1%(n=6)were obtained from agatroban samples at three spiked levels of IBCF(2.50,25.00,50.00 μg/g),which showed good accuracy of this method.Good precision of detection results was obtained by different laboratory technicians at different times,the mean value of spiked sample solution(25.00 μg/g)was 24.28 μg/g,and the RSD was 2.1%(n=12).The durability was good,minor changes of detection conditions had little effect on the results.Under the original condition and conditions with initial column temperature±5℃,heating rate±2℃/min,column flow rate±0.1 mL/min,the IBCF content of spiked sample solution(25.00 μg/g)was detected,the mean value of detection results was 24.16 μg/g,and the RSD was 2.2%(n=7).Eight batches of agatroban samples from two manufacturers were detected using the established method,and the results showed that no IBCF residue was detected in any of these samples.The agatroban samples could be dissolved by methanol,and then the IBCF residue could be simultaneously extracted and derived with methanol as well.This detection method had the advantages of simple operation,high sensitivity,low matrix effect and accurate quantification,which provided a new effective method for detection of IBCF residue in agatroban.
