March 3–6, 2008, PITTCON® 2008, New Orleans, LA, USA

Chromatographic Method Development: An Approach Incorporating UPLC, MS and Modeling Software to Streamline the Process of Creating Robust Methods

Lauren Wood (Waters) and Mike McBrien (ACD/Labs)

Abstract

This study demonstrates the utility of Ultra Performance Liquid Chromatography (UPLC) technology, single quadrupole MS and chromatographic modeling software to facilitate an efficient method development process of impurity profiles for pharmaceutical drug entities. The HPLC method for Simvastatin has been redeveloped on UPLC to be compatible for MS. The analytical goals were to meet the requirements stated in the USP 30 - NF 25 monograph for the Simvastatin drug substance and drug product chromatographic purity and assay identification. Chromatographic modeling software was used to aid in the iterative method development decision-making process by systematically assessing method parameters such as stationary phase, solvent, temperature, pH, gradient, and mobile phase additives during both the screening and optimization steps of method development. This software was also used to automatically program the predicted instrument conditions in the chromatography data system (CDS) software, thus automating instrument control. UV and MS Peak Matching routines were used to identify and match peaks between injections and datasets based on spectral similarity between components. User-defined mathematical calculations and specialized reports were also used in streamlining the decision-making process during method development. The use of UPLC in combination with single quadrupole MS with electrospray positive/negative ionization detection aids in the discovery of any impurities which contain no chromaphores. Pre-validation of the methodology to verify specificity, linearity, accuracy, and precision was also performed for verification of method conversion equivalency.

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Relevant Products: ACD/AutoChrom, ACD/Method Development Suite for LC/MS

Relevant Solution: Chromatography