Zhou Lili, Mao Bing, Reamer Robert, Novak Tom, Ge Zhihong
Merck Research Laboratories, Early Development Analytical Research, P.O. Box 2000, RY818-B225, Rahway, NJ 07065, USA.
J Pharm Biomed Anal. 2007 Jun 28;44(2):421-9. doi: 10.1016/j.jpba.2006.11.004. Epub 2006 Dec 4.
Tracking the impurity profile of an active pharmaceutical ingredient (API) is a very important task for all stages of drug development. A systematic approach for tracking impurity profile of API is described. Various real pharmaceutical applications are presented through successful examples of impurity profile tracking for three different novel APIs. These include MK-0969, an M3 antagonist; MK-0677, an oral-active growth hormone secretagogue and API-A, a cathepsin K inhibitor. A general strategy including selection of a reversed phase high performance liquid chromatographic (RP-HPLC) impurity profile method based on screening various stationary phases and changing the pH of the mobile phase and elucidation of impurity structures through the utilization of LC-MS, preparative-LC and NMR is demonstrated. A series of studies were conducted on the peak purity check by using the LC-UV diode-array and LC-MS detections. The advantages and disadvantages of each technique in the evaluation of peak purity are discussed.
追踪活性药物成分（API）的杂质概况对于药物研发的各个阶段而言都是一项非常重要的任务。本文描述了一种追踪API杂质概况的系统方法。通过三种不同新型API杂质概况追踪的成功案例展示了各种实际制药应用。这些API包括M3拮抗剂MK-0969、口服活性生长激素促分泌剂MK-0677以及组织蛋白酶K抑制剂API-A。本文展示了一种通用策略，包括基于筛选各种固定相和改变流动相pH值来选择反相高效液相色谱（RP-HPLC）杂质概况方法，以及通过利用液相色谱-质谱联用（LC-MS）、制备液相色谱（preparative-LC）和核磁共振（NMR）来阐明杂质结构。利用液相色谱-紫外二极管阵列（LC-UV diode-array）和LC-MS检测对峰纯度检查进行了一系列研究。讨论了每种技术在评估峰纯度方面的优缺点。
