title: Efficient HPLC method development using structure-based database search, physico-chemical prediction and chromatographic simulation.
abstract: Development of a robust HPLC method for pharmaceutical analysis can be very challenging and time-consuming. In our laboratory, we have developed a new workflow leveraging ACD/Labs software tools to improve the performance of HPLC method development. First, we established ACD-based analytical method databases that can be searched by chemical structure similarity. By taking advantage of the existing knowledge of HPLC methods archived in the databases, one can find a good starting point for HPLC method development, or even reuse an existing method as is for a new project. Second, we used the software to predict compound physicochemical properties before running actual experiments to help select appropriate method conditions for targeted screening experiments. Finally, after selecting stationary and mobile phases, we used modeling software to simulate chromatographic separations for optimized temperature and gradient program. The optimized new method was then uploaded to internal databases as knowledge available to assist future method development efforts. Routine implementation of such standardized workflows has the potential to reduce the number of experiments required for method development and facilitate systematic and efficient development of faster, greener and more robust methods leading to greater productivity. In this article, we used Loratadine method development as an example to demonstrate efficient method development using this new workflow.
authors.affiliation: Merck Research Laboratories, Merck, Rahway, NJ 07065, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Merck Manufacturing Division, Merck, Rahway, NJ 07065, USA. Electronic address: jinjian.zheng@merck.com.
authors.forename: Jinjian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Merck Research Laboratories, Merck, Rahway, NJ 07065, USA.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Gong
authors.affiliation: Merck Manufacturing Division, Merck, Rahway, NJ 07065, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Hartman
authors.affiliation: Merck Research Laboratories, Merck, Rahway, NJ 07065, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Antonucci
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003198:Computer Simulation; D062126:Databases, Chemical; D017336:Loratadine / Q000737:chemistry; D015394:Molecular Structure; D012984:Software
chemical_list: D017336:Loratadine
keywords: ACD/Labs; Chromatographic simulation; HPLC; Loratadine; Physico-chemical prediction