Discussion on the dimerization reaction of penicillin antibiotics  

作　　者：Qizhang Wu Xia Zhang Jiaxin Du Changqin Hu 

机构地区：[1]National Institutes for Food and Drug Control,Beijing,102629,China

出　　处：《Journal of Pharmaceutical Analysis》2022年第3期481-488,共8页药物分析学报（英文版）

基　　金：supported by the National Major Scientific and Technological Special Project for“Significant New Drugs Development”(Grant No.:2017ZX09101001-007).

摘　　要：Penicillins are one type of the most important antibiotics used in the clinic.Control of drug impurity profiles is an important part of ensuring drug safety.This is particularly important in penicillins where polymerization can lead to polymers as elicitors of passive cutaneous anaphylaxis.The current understanding of penicillin polymerization is based on reactions with amino groups,but no comprehensive mechanistic understanding has been reported.Here,we used theoretical calculations and column switching-LC/MS techniques to study penicillin dimerization.Ampicillin and benzylpenicillin were selected as representative penicillins with or without amino groups in the side chain,respectively.We identified four pathways by which this may occur and the energy barrier graphs of each reaction process were given.For benzylpenicillin without an amino group in the 6-side chain,dimerization mode A is the dominant mode,where the 2-carboxyl group of one molecule reacts with the b-lactam of another molecule.However,ampicillin with an amino group in the 6-side chain favors dimerization mode C,where the amino group of one molecule attacks the b-lactam of another molecule.These findings can lead to a polymer control approach to maintaining penicillin antibiotics in an active formulation.

关 键 词：PENICILLINS Dimerization reaction Theoretical calculations LC/MS 

分 类 号：R91[医药卫生—药学]