Drug substance manufacture process control: Application of flow injection analysis and HPLC for monitoring an enantiospecific synthesis

被引：4

作者：

Chong, K ^{[1
]}

Loughlin, T ^{[1
]}

Moeder, C ^{[1
]}

Perpall, HJ ^{[1
]}

Thompson, R ^{[1
]}

Grinberg, N ^{[1
]}

Smith, GB ^{[1
]}

Bhupathy, M ^{[1
]}

Bicker, G ^{[1
]}

机构：

[1] MERCK RES LABS,RAHWAY,NJ 07065

来源：

JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS | 1996年 / 15卷 / 01期

关键词：

diastereomers; enantiomeric separation; enzyme activity; flow injection;

D O I：

10.1016/0731-7085(96)01810-9

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD(4) antagonist. In a key step of the compound's synthesis, a prochiral diester intermediate undergoes an enantioselective enzymatic hydrolysis (in the presence of Triton X-100) leading to the (S)-ester acid. Subsequent processing transforms the ester acid into the final product. The residual amount of the detergent in the final product, the rapid determination of the enzymatic activity and the optical purity of the final product emerged as key issues in the control of the reaction. As a solution, two techniques were utilized and are presented: flow injection analysis and HPLC.

引用

页码：111 / 121

页数：11

共 36 条

[1] STEREOCHEMISTRY - A SOURCE OF PROBLEMS IN MEDICINAL CHEMISTRY [J].