Determination of bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride by UPLC-MS/MS
10.16438/j.0513-4870.2020-1937
- VernacularTitle:UPLC-MS/MS法测定盐酸曲唑酮片剂中遗传毒性杂质双 (2-氯乙基) 胺盐酸盐和1-(3-氯苯基)-4-(3-氯丙基) 哌嗪盐酸盐
- Author:
Jun-yue WAN
1
;
Hua CHEN
2
;
Jie YIN
2
Author Information
1. China Pharmaceutical University, Nanjing 210000, China
2. NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs, National Institutes for Food and Drug Control, Beijing 100050, China
- Publication Type:Research Article
- Keywords:
UPLC-MS/MS;
trazodone hydrochloride;
genotoxic impurity;
bis(2-chloroethyl)amine hydrochloride;
1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride
- From:
Acta Pharmaceutica Sinica
2021;56(5):1439-1443
- CountryChina
- Language:Chinese
-
Abstract:
An UPLC-MS/MS method was established for the quantification of the genotoxic impurities bis(2-chloroethyl)amine hydrochloride and 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in trazodone hydrochloride. The chromatographic separation of the two genotoxic impurities was performed on Waters ACQUITY UPLC BEH C18 column (100 mm×2.1 mm, 1.7 μm) at 20 ℃. A mixture of 5 mmol·L-1 ammonium hydrogen carbonate aqueous solution and acetonitrile at a flow rate of 0.3 mL·min-1 in gradient elution mode was employed as mobile phase. The UPLC-MS/MS was equipped with electrospray ionization in positive ionization mode and adopted multiple reaction monitoring mode. We found that the calibration curves of the two genotoxic impurities were linear in the range of 0.1-10 ng·mL-1. The limit of detection was 0.10 ng·mL-1 for bis(2-chloroethyl)amine hydrochloride and the average recovery was 101.53% (RSD = 4.06%). The limit of detection was 0.01 ng·mL-1 for 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride and the average recovery was 97.95% (RSD = 1.27%). The sample solution was stable for 24 h. No bis(2-chloroethyl)amine hydrochloride was detected in the samples, and the content of 1-(3-chloropropyl)-4-(3-chlorophenyl)piperazine hydrochloride in the samples was within the limit. This research provides a method to improve the quality control standards of trazadone.
