Page 156 - 《精细化工》2020年第9期

第 37 卷第 9 期 精 细 化 工 Vol.37, No.9
202 0 年 9 月 FINE CHEMICALS Sept. 2020

医药与日化原料
磺胺二甲嘧啶-对羟基苯甲酸共晶

在乙腈溶剂中的三元相图测定

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刘文举，姚甜甜，申艳敏 ，孙 晨，徐金杰
（河南工业大学 化学化工学院，河南 郑州 450001）

摘要：建立一种 HPLC 同时分析测定溶液中磺胺二甲嘧啶和对羟基苯甲酸含量的方法，结果表明，以乙腈-磷酸
水溶液（pH=3.15）为流动相，两者体积比为 18∶82 时，能使磺胺二甲嘧啶和对羟基苯甲酸在 9 min 内迅速分
离，该法精密度和稳定性的相对标准偏差（RSD）均小于 2%，磺胺二甲嘧啶和对羟基苯甲酸的平均回收率分别
为 98.73%、98.90%。在该基础上，采用溶液法制备磺胺二甲嘧啶-对羟基苯甲酸共晶，分别在 298.15、303.15 K
时，建立共晶体在乙腈中的三元相图。采用 XRD、DSC、SEM 对磺胺二甲嘧啶、对羟基苯甲酸和在 298.15 K
时部分干燥固相进行表征分析。结果表明，磺胺二甲嘧啶-对羟基苯甲酸-乙腈体系相图是对称相图，随着温度的
升高，磺胺二甲嘧啶-对羟基苯甲酸共晶区域增大，有利于共晶的形成，可根据相图的规律性制备磺胺二甲嘧啶-
对羟基苯甲酸共晶，提高磺胺二甲嘧啶的溶解度。
关键词：磺胺二甲嘧啶；对羟基苯甲酸；高效液相色谱；三元相图；共晶；医药原料
中图分类号：R917 文献标识码：A 文章编号：1003-5214 (2020) 09-1870-07

Determination of ternary phase diagram of sulfamethazine-p-
hydroxybenzoic acid cocrystal in acetonitrile solvent

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LIU Wenju, YAO Tiantian, SHEN Yanmin , SUN Chen, XU Jinjie
（College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450001, Henan,
China）

Abstract: A HPLC method for the simultaneous determination of sulfamethazine and p-hydroxybenzoic
acid in solution was established. The results showed that when the mobile phase consisted of acetonitrile
and phosphoric acid aqueous solution (pH=3.15) with a volume ratio of acetonitrile to phosphoric acid
aqueous solution of 18∶82, sulfamethazine and p-hydroxybenzoic acid could be quickly separated in 9
minutes. The relative standard deviation (RSD) of precision and stability of this method was less than 2%.
The average recoveries of sulfamethazine and p-hydroxybenzoic acid were 98.73% and 98.90%,
respectively. On this basis, the sulfamethazine-p-hydroxybenzoic acid cocrystal was prepared by solution
method. At 298.15 and 303.15 K, the ternary phase diagram of the cocrystal in acetonitrile was established.
XRD, DSC and SEM were used to characterize sulfamethazine, p-hydroxybenzoic acid and partially dried
solid phase at 298.15 K. The results revealed that the phase diagram of sulfamethazine- p-hydroxybenzoic
acid-acetonitrile system was symmetrical. With the increase of temperature, the
sulfamethazine-p-hydroxybenzoic acid cocrystal region increased, which is beneficial to the formation of
cocrystals. Sulfamethazine-p-hydroxybenzoic acid cocrystals could be prepared by regulating the phase
diagram to improve the solubility of sulfamethazine.
Key words: sulfadimidine; p-hydroxybenzoic acid; HPLC; ternary phase diagram; cocrystal; drug materials

收稿日期：2020-03-04; 定用日期：2020-04-21; DOI: 10.13550/j.jxhg.20200166
基金项目：河南省科技攻关项目（202102310208，182102210399）；河南工业大学科技创新人才培育计划（2017rcjh09，2017QNJH29）
作者简介：刘文举（1980—），女，副教授，E-mail：wenjuliu@haut.edu.cn。联系人：申艳敏（1978—），女，讲师，E-mail：
shenym1678@126.com。