« CHROMATOGRAPHY
are not limited to, sampling rate and fraction volume from the 1st D, the loop size, organic and buff er strengths in diff erent fractions, and solvent compatibility between two dimensions. At the same time, the components, impurities and degradation products in pharmaceutics could have a wide range of physical and chemical properties. To turn 2DLC from a special research tool into routine use, especially in a regulated environment, a platform 2DLC strategy is highly desirable, including instrumentation, software and implementation strategy. The platform strategy is particularly desirable for pharmaceutical analysis, where reproducibility, accuracy, sensitivity, robustness and method transferability are critical factors. A generic platform 2DLC strategy with easy-to-use software and hardware will provide the busy analysts a solution or at least a readily available starting point for their applications.
Summary
2DLC greatly enhances the separation power of one-dimensional separation.
The interest in 2DLC in pharmaceutical analysis
has increased rapidly in recent years due to the advances and commercialization of 2DLC hardware, software, and new column technologies. 2DLC has been applied to address pharmaceutical challenges such as resolving peak co-elution, impurity quantifi cation, peak purity assessment, stability-indicating method development, 2DLC-MS, chiral separation, etc. A platform strategy is highly desirable when using 2DLC routinely. An increase in 2DLC applications for pharmaceutical analysis is expected in the years to come.
Figure 5. 2DLC separation and quantifi cation of an impurity that co-eluted with the main peak in the fi rst dimension
Author Biographies 6. Chiral Separation
Using one dimension to separate achiral impurities or matrix and the other dimension to separate enantiomers or derivatives have been reported for 2DLC chiral separation of amphetamine , pantoprazole and lansoprazole , and for the determination of enantiomeric excess in reaction mixtures [26-28]. There are also applications reported for chiral separation of amino acids [29, 30].
7. Others
2DLC can also be used as a tool to remove sample matrix, and thus to reduce the sample preparation or purifi cation work [8, 28, 31]. Other 2DLC applications have included preparative scale separation and purifi cation, on-line concentration for the analysis of low-level impurities [32, 33].
Platform 2DLC Strategy
2DLC method development is much more complicated than 1DLC. In addition to the factors that must be considered in 1DLC, many more factors are involved in 2DLC method development. These include, but
Kelly Zhang, Ph.D., is a Scientist in the Small Molecule Analytical Chemistry and Quality Control group at Genentech. She obtained her Ph.D. in Analytical Chemistry in 1999 from Wuhan University, China. Prior to joining Genentech in 2007, she was a Senior Scientist at Allergan and Pfi zer.
Jenny Wang M.S., is a Research Associate in the Small Molecule Analytical Chemistry and Quality Control group at Genentech. She was formerly Scientist/Associate Scientist at Allergan, Arena Pharmaceutical and Pfi zer. She holds a Master’s degree in Chemistry from the University of Scranton.
Midco Tsang B.S., is a Research Associate in the Small Molecule Analytical Chemistry and Quality Control group at Genentech. She earned a B.S. in Biochemistry from California State University. Her research interests involve HPLC method development for chiral and achiral pharmaceutical compounds and 2DLC. She was an analytical chemist for Chevron Corporation.
Larry Wigman Ph.D., is an Analytical Chemist by training with his doctorate from Duke University. Larry has held various positions including: Senior Research Scientist at Pfi zer, Manager at Mylan, Associate Director at Sanofi , Principal Consultant at Regulitics LLC; and, most recently
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