Elemental impurities determination in bromhexine hydrochloride injections

Shujuan Xu; Lei Zhang; Qingshan Bai; Lihua Wang; Xiao Chen

doi:10.1016/j.jpba.2023.115379

Elemental impurities determination in bromhexine hydrochloride injections

J Pharm Biomed Anal. 2023 May 30:229:115379. doi: 10.1016/j.jpba.2023.115379. Epub 2023 Mar 30.

Authors

Shujuan Xu¹, Lei Zhang², Qingshan Bai², Lihua Wang², Xiao Chen²

Affiliations

¹ Linyi Inspection and Testing Center, Linyi 276000, China. Electronic address: junyingcaoxsj@163.com.
² Linyi Inspection and Testing Center, Linyi 276000, China.

PMID: 37011549
DOI: 10.1016/j.jpba.2023.115379

Abstract

Elemental impurities in drug products have no therapeutic effect and may pose toxicological concerns, therefore it is urgent to assess the safety of elements especially in parenteral exposure drug. In the present work, a high throughput inductively coupled plasma mass spectrometry (ICP-MS) method was developed for the quantitative determination of 31 elemental impurities in bromhexine hydrochloride injections from 9 manufactures. The method was successfully validated for linearity, accuracy, precision, stability, the LOD and the LOQ according to the United States Pharmacopeia (USP) < 233 > . All the elemental impurities determined were below the permitted daily exposure (PDE) limits proposed by the International Council for Harmonisation (ICH). However, significant differences were found between different manufactures' products for some elements, particularly for Al, As, B, Ba and Zn. Besides, discussions considering potential risks of elemental contamination were also presented.

Keywords: Bromhexine hydrochloride injections; Elemental impurities; Inductively coupled plasma mass spectrometry; International Council for Harmonisation; Quantitative determination.

MeSH terms

Drug Contamination*
Mass Spectrometry / methods
Spectrum Analysis