Qiu Fenghe, Pennino Scott, Busacca Carl A, Norwood Daniel L
Department of Analytical Sciences, Boehringer Ingelheim Pharmaceuticals Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
J Pharm Biomed Anal. 2009 Apr 5;49(3):733-8. doi: 10.1016/j.jpba.2009.01.010. Epub 2009 Jan 20.
Impurities in pharmaceutical products do not enhance the desired therapeutic effect and may, of course, have adverse effects. Impurities must therefore be limited or controlled for quality and safety considerations. Structural identification of an impurity is the first step in understanding the chemistry of its formation and subsequently controlling the impurity. In this article, the chemical structure of an unknown by-product formed during the synthesis of a nevirapine analogue HIV NNRT inhibitor was identified using a combination of low resolution, high resolution and H/D exchange LC/MS and LC/MS/MS. The origin of the impurity was investigated through a series of photo- and oxidative stress studies. It was concluded that this impurity is formed via a side-reaction of the last intermediate with the oxidant used in the synthesis.
药品中的杂质不会增强预期的治疗效果，当然，还可能产生不良反应。因此，出于质量和安全考虑，必须对杂质进行限制或控制。杂质的结构鉴定是了解其形成化学过程并随后控制该杂质的第一步。在本文中，使用低分辨率、高分辨率以及H/D交换LC/MS和LC/MS/MS相结合的方法，鉴定了奈韦拉平类似物HIV非核苷类逆转录酶抑制剂合成过程中形成的一种未知副产物的化学结构。通过一系列光应激和氧化应激研究对该杂质的来源进行了调查。得出的结论是，该杂质是通过最后一种中间体与合成中使用的氧化剂发生副反应形成的。
