Content Determination of 20 Element Impurities in Aminomethylbenzoic Acid Injections and Its Compatibility Investigation
- VernacularTitle:氨甲苯酸注射液中20种元素杂质的含量测定及相容性考察
- Author:
Hai HUANG
1
;
Yaowen ZHANG
1
;
Jiaxuan SONG
2
;
Ming YU
1
;
Wankui XU
1
Author Information
1. Liaoning Institute for Drug Control/ Liaoning Province Inspection and Testing Certification Center，Shenyang 110035，China
2. Dept. of Pediatrics，General Hospital of Northern Theat er Co mmand，Shenyang 110016，China
- Publication Type:Journal Article
- Keywords:
Aminomethylbenzoic acid injection;
ICP-MS
- From:
China Pharmacy
2021;32(11):1330-1336
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE：To establish a m ethod to determine the cont ents of 20 elements impurities in Aminomethylbenzoic acid injection ，and to investigate its compatibility in low-borosilicate glass ampoules. METHODS ：The sample was diluted with 5％ nitric acid solution ，and then determined by ICP-MS using scandium ，indium and bismuth as internal standards. The nebulizer flow（argon）was 0.92 L/min，collision gas flow （helium）was 4.5 L/min，RF power was 1 895 W，plasma flow was 18 L/min， pump speed was 40 r/min，injection delay time was 65 s. The collision mode was used as measurement mode ，the data sampling adopted peak skipping mode ，and repeated for 3 times. The accelerated test was carried out after sample was stored at 70 ℃ for 1 and 3 months，and the compatibility was investigated by comparing the change trend of element impurity content. RESULTS ：The linear range of vanadium ，cobalt，chromium，arsenic，cadmium，antimony，mercury，thallium and lead were 0.01-20 μg/L；those of magnesium ，aluminium，ferrum，nickel，copper，zinc，barium were 0.1-200 μg/L；those of boron ，silicon，potassium and calcium were 1-2 000 μg/L（r≥0.999 8）. RSDs of precision ，intermediate precision ，stability（8 h）and repeatability test were all lower than 6％. The limits of quantitation were 0.000 7-2.986 3 μg/L；the limits of detection were 0.000 2-0.895 9 μg/L. The average recoveries were 88.50％-111.00％（RSDs were 0.52％-2.33％，n＝9）. The minimum content of 20 element impurities was less than detection limits ，the maximum contents were 3 835.9 μg/L（0 month），10 448.4 μg/L（1 month），17 261.2 μg/L（3 month） in Aminomethylbenzoic acid injection from 8 manufacturers. Among the 20 elements impurities ，except that boron ， aluminum，magnesium，silicon，calcium and potassium were not specified ，the contents of other elements were less than the threshold. The research of compatibility showed that the impurity contents of seven elements such as boron ，aluminum，silicon， potassium，zinc，arsenic and barium showed an increasing trend. The silicon concentration ，silicon/aluminum concentration ratio and silicon/boron concentration ratio in the accelerated samples after stored for one and three months were significantly different from those stored for 0 month. CONCLUSIONS ：The established method is sensitive ，reproducible and accurate ，and can be used for the content determination of 20 element impurities in Aminomethylbenzoic acid injection. The interaction between low-borosilicate ampoule and Aminomethylbenzoic acid injection is obvious.
