Optimization and Standardization of Liquid Chromatography‐Mass Spectrometry Systems for the Analysis of Drug Discovery Compounds

Standardization of Analytical Methodology and Procedures for Purity Assessment of Small Molecules in Drug Discovery

“…Electrospray mass spectrometry measurements were performed on a MSD quadrupole mass spectrometer (Agilent Technologies, Palo Alto, CA, USA) interfaced to the HP1200 or HP1100 HPLC system. MS measurements were acquired simultaneously in both positive and negative ionization modes (fragmentor 120 V, threshold spectral abundance 150, MS peak width 0.09 minutes) over the mass range of 100-800 (12). Data acquisition and integration for LC-UV and MS detection were collected using Chemstation software (Agilent Technologies).…”

“…The benefits of orthogonal reversed-phase LC-MS-based methods, to accurately determine the identity and purity of drug discovery compounds have been recently discussed by our group (3). Additionally, an approach for improving the speed and effectiveness of orthogonal low and high pH LC-MS for routine purity assessment on a single system was demonstrated and standardized across two different sites within Lilly Research Laboratories (12).…”

“…We have continued our previous strategy for developing LC-MS methods (3,12) with the evaluation of different chromatographic approaches for improving the speed and effectiveness of orthogonal LC-MS methods for routine purity assessment under an open access environment (analysis carried out by chemists with minimum training on sample submission). Starting with our optimized 7 min LC-MS gradients (12), more effective and faster methods with higher resolution power were projected to reduce the analysis cycle time without sacrificing data quality.…”

“…Starting with our optimized 7 min LC-MS gradients (12), more effective and faster methods with higher resolution power were projected to reduce the analysis cycle time without sacrificing data quality. Advantages and disadvantages of 4 column technologies (Gemini NX C18, XTerra MS C18, Atlantis dC18 and Kinetex C18) were evaluated in comparison with conventional Gemini C18 and XBridge C18 columns.…”

Orthogonal analytical screening for liquid chromatography–mass spectrometry method development and preparative scale-up

“…For instance, it has been found that the use of orthogonal separation procedures reduces the risk of incorrect purity assessment of drug compounds and ensures the quality and safety of drug products. This can be achieved by changing pH, organic solvents, aqueous buffer and stationary phases [13][14][15][16]. Several elegant approaches have been used to automate this method searching.…”