Determination of Trace N-nitrosopropranolol in Propranolol Hydrochloride Sustained Release Tablets by UHPLC-Q-Orbitrap HRMS
10.3870/j.issn.1004-0781.2025.04.020
- VernacularTitle:超高效液相色谱-四极杆静电场高分辨质谱联用法测定盐酸普萘洛尔缓释片中痕量N-亚硝基普萘洛尔
- Author:
Changchuan GUO
1
;
Songsong WEN
;
Dengyi LYU
;
Weijian WANG
;
Shujuan YANG
;
Chong NIU
;
Yuwen XU
Author Information
1. 山东省食品药品检验研究院、国家药品监督管理局仿制药研究与评价重点实验室、山东省仿制药一致性评价工程技术研究中心、经皮给药系统山东省工程研究中心、产业技术基础公共服务平台,济南 250101
- Publication Type:Journal Article
- Keywords:
N-nitrosopropranolol;
Genotoxicity;
Impurity;
High-resolution mass spectrometry;
Ultrahigh-performance liquid chromatography;
Determination of content
- From:
Herald of Medicine
2025;44(4):628-633
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish a ultrahigh-performance liquid chromatography-orbitrap high-resolution mass spectrometry(UHPLC-Orbitrap HRMS)method for the determination of the genotoxic impurity N-nitroso propranolol(NPPN)in propranolol hydrochloride sustained-release tablets.Methods The test sample was ultrasonically extracted using methanol as the solvent,then centrifuged and filtered before injection analysis.Chromatographic separation was performed using a 2.7 μm particle size C18 UHPLC column with a mobile phase of 0.1％formic acid(A)in water and 0.1％formic acid(B)in acetonitrile,using gradient elution.Mass spectrometry was conducted with an HESI ion source in positive ion parallel reaction monitoring(PRM)scan mode,monitoring the NPPN fragment ion at m/z 72.080 8,and quantification was performed using the standard curve method.Results The calibration curve was in good linearity in the range of 0.51-20.30 ng·mL-1 with excellent correlation coefficient(r)of 0.9999.The recoveries of NPPN at three levels(low,medium,and high)were in the range of 95.4％～98.3％,while the RSDs were from 2.5％to 4.2％.The limit of detection(LOD)was 0.20 ng·mL-1 while the limit of quantitfication(LOQ)was 0.51 ng·mL-1.This analytical method was used to determine NPPN in six batches of propranolol hydrochloride sustained release tablet samples.NPPN was detected in all six samples,among which the detection amount of 3 batches have exceeded the acceptable limit.Conclusion This method is sensitive,accurate,and fast,making it useful for pharmaceutical companies in controlling production processes and providing robust technical support for regulatory authorities.
