Zhou Lili, Welch Chris, Lee Clair, Gong Xiaoyi, Antonucci Vincent, Ge Zhihong
Merck Research Laboratories, Merck & Co Inc, Rahway, NJ 07065, USA.
J Pharm Biomed Anal. 2009 May 1;49(4):964-9. doi: 10.1016/j.jpba.2009.02.021. Epub 2009 Feb 28.
The enantioselectivity of a collection of neutral pharmaceutical compounds on six different types of polysaccharide chiral stationary phases (CSPs), Chiralpak AD (and AD-RH), Chiralcel OD (and OD-RH), Chiralpak OJ (and OJ-R), Chiralcel AS (and AS-RH), Sepapak-2 and Sepapak-4 are compared using reversed phase (RPLC) and normal phase liquid chromatography (NPLC). Screening strategies for maximizing the probability of achieving an initial chiral separation hit for neutral compounds using both RPLC and NPLC are described. Further method optimizations are demonstrated by modifying parameters such as organic modifier composition, eluent pH or CSP particle size. Several practical examples of the application of chiral methods for the study of synthetic reaction mixtures are presented. The most critical validation aspects, including limit of detection, specificity, and ruggedness, are also briefly presented.
使用反相（RPLC）和正相液相色谱（NPLC）比较了一组中性药物化合物在六种不同类型的多糖手性固定相（CSP）上的对映选择性，这些固定相包括Chiralpak AD（和AD-RH）、Chiralcel OD（和OD-RH）、Chiralpak OJ（和OJ-R）、Chiralcel AS（和AS-RH）、Sepapak-2和Sepapak-4。描述了使用RPLC和NPLC最大化中性化合物实现初始手性分离成功概率的筛选策略。通过修改有机改性剂组成、洗脱液pH值或CSP粒径等参数展示了进一步的方法优化。给出了手性方法用于合成反应混合物研究的几个实际应用示例。还简要介绍了最关键的验证方面，包括检测限、特异性和耐用性。
