Adsorption of Amine Compounds on the Glass Surface and Their Impact on the Development of Analytical Method and Pharmaceutical Process

• Published in: Organic process research & development Vol. 26; no. 2; pp. 431 - 436
• Main Authors: Xu, Xuejun, Lott, Jennifer, Kelly, Kathleen A, Shi, Zhongping
• Format: Journal Article
• Language: English
• Published: American Chemical Society 18.02.2022
• Subjects: diamine; adsorption; LC-MS; glass surface
• ISSN: 1083-6160; 1520-586X
• DOI: 10.1021/acs.oprd.1c00451

A diamine compound (3-{2-[2-(3-aminopropoxy)­ethoxy]­ethoxy}­propan-1-amine) was demonstrated to impact downstream steps in a pharmaceutical synthetic process, and control of this compound to less than 0.015 wt % (or 150 ppm) was necessary. A novel, simple, and sensitive liquid chromatography/mass spectrometry (LC/MS) method without the derivatization of the diamine was developed for in-process control (IPC) and demonstrated to be suitable for use when experiments were run at a small lab scale. During the development of the LC-MS method, the diamine was found to significantly adsorb to the surface of glassware, and the adsorption constant was estimated to be (5.4–10.4) × 108 mL/mol SiOH. This phenomenon impacted the analytical method recovery and the control of the diamine in the process. The diamine adsorption was investigated, and procedures were developed to mitigate adsorption. The addition of 0.1% triethylamine in sample diluent was found to significantly reduce adsorption of the diamine and improve LC-MS method recovery. However, at the kilo plant scale, the impurities that were initially inhibited in development work appeared. It was determined that the diamine adsorbed on glassware more strongly than previously expected, including the reactor. This paper will discuss steps taken to reduce adsorption on glass for both the analytical scale and the plant glass reactor.