44


September 2009


Modern Chiral Separations using HPLC and SFC forMethod Development and Prep Purification


by GARYW. YANIK (gwyanik@pdr-chiral.com) and Irene Tranquil (itranquil@pdr-chiral.com) PDR-Chiral Inc., 1331A South Killian Drive, Lake Park, FL 33418, USA.


This article discusses factors important to operating a fast (high throughput) and efficient HPLC/SFC method development and prep purification laboratory. Discussion will include procedures for quickly developing separation methods and purifying pharmaceutical candidates as well as the systems, instruments, columns, and solvents we use to develop methods and purify samples in one week. Select examples will be presented.


Key words: Chiral, Chiral Separations, HPLC, SFC, Method Development, Prep Purification


Introduction Competitive and economic factors are driving pharmaceutical companies towards increased efficiency and cost reduction. Most new pharmaceutical candidates produced by medicinal chemistry need to be analyzed and purified by HPLC/SFC quickly in order to decide which compounds are worth further development – often creating a throughput bottleneck.


In order to develop a goodmethod youmust start with a well chosen set of columns and solvents and screen a productive variety of conditions to determine the bestmethod for a particular compound. An example of useful columns and solvents are listed in Table 1 below. Other useful columns aremanufactured by companies including Phenomenex, Regis, Kromasil, and ASTEC (now Supelco). Similarly other solvents can prove useful, but if toomany conditions are screened the time to screen becomes unrealistically long. This realistic


example is intended to illustrate bounding the number ofmethods to be screened and should not be interpreted as the correct answer for all applications.


Experimental A description of our experimental conditions and results are presented below and divided into 3 sections:Method Screening & Optimization, Preparative Purification, and Chiral Detection. All experimental work was done in our labs over the last few years.


Method Screening & Optimization Amodernmethod screening systemflow diagramis illustrated in Figure 1 and an example is pictured below in Figure 2. The


Figure 1: Method Screening Flow Diagram


Table 1: Example of useful columns and solvents for chiral HPLC and SFC screening


Figure 2: AutoMDS on Agilent 1100 with 22 Columns & 20 Bottles


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