Feasibility study on mercury-free green testing of hydrochloride salt drugs in the Chinese Pharmacopoeia

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Author:  LIU Huiying LI Shangying HUANG Hai XU Wankui

Affiliation: Liaoning Institute for Drug Control, Liaoning Inspection, Testing and Certification Center, State Key Laboratory of Chemical Drug Quality Research and Evaluation, Shenyang 110023, China

Keywords: Hydrochloride drugs Method substitution Mercury salt elimination Green drug testing Quality control

DOI: 10.12173/j.issn.2097-4922.202503074

Reference: LIU Huiying, LI Shangying, HUANG Hai, XU Wankui. Feasibility study on mercury-free green testing of hydrochloride salt drugs in the Chinese Pharmacopoeia[J]. Yaoxue QianYan Zazhi, 2025, 29(5): 756-763. DOI: 10.12173/j.issn.2097-4922.202503074.[Article in Chinese]  Copied

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Abstract

Objective To explore the substitution method for the mercuric acetate-based non-aqueous titration with hydrochloride salt drugs in national drug standards, in order to address the environmental pollution issues caused by the use of mercury salts, and promote the development of green pharmaceutical testing.

Methods Rimantadine hydrochloride, betahistine hydrochloride, clonidine hydrochloride, lysine hydrochloride, and berbamine hydrochloride were as the study subjects, diverse titration and chromatographic methodologies were used to explore the method substitution, and the comprehensive analysis of multiple varieties was conducted to investigate the principles of the selection of alternative analytical approaches.

Results Solvent system optimization could demonstrate significant expansion of the applicability scope for sodium hydroxide titration methodology. However, in the perchloric acid titration of lysine hydrochloride, the introduction of mercuric acetate was found to induce a positive bias in analytical results. There were no statistically significant discrepancies between alternative methods and current national standard protocols for rimantadine hydrochloride, betahistine hydrochloride, and clonidine hydrochloride (P>0.05) , whereas method validation for lysine hydrochloride and berbamine hydrochloride exhibited marked deviations (P<0.05).

Conclusion The current national standards for lysine hydrochloride and berbamine hydrochloride require revision and modernization. It is feasible to adopt mercury-free alternative methods for the determination of national drug standards. The National Pharmacopoeia Commission should conduct research on method substitution for relevant varieties and revise the relevant standards as soon as possible.

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