title: Enhanced performance test mix for high-throughput LC/MS analysis of pharmaceutical compounds.
abstract: LC/MS is being used for the routine analysis of small molecules in both the discovery and development stages within the pharmaceutical industry. In drug discovery, LC/MS is relied upon to confirm the identity and assess the purity of chemical entities. To ensure the quality of LC/MS analysis, it is important that the LC/MS system is operating within defined performance criteria. Performance monitoring of the system with a standard compound mix offers many advantages over other alternatives, since it monitors the LC/MS system as an integrated unit under the same working conditions as those used for the analysis of samples. It is also a convenient approach, because the test mix can be injected as part of the automated sequence. Use of a test mix for similar purposes has been described previously (Tang, L.; Fitch, W. L.; Alexander, M. S.; Dolan, J. W. Anal. Chem. 2000, 72, 5211-5218). To monitor the performance of ArQule's LC/MS operation (with UV and ELS detection) in greater detail, a set of eight compounds was selected from a collection of 137 commercially available "druglike" compounds. The compounds are generally stable and compliant with the rule-of-five criteria. This enhanced mix has a balanced selection of pKa values and covers the typical range of hydrophobicity and molecular masses of pharmaceutical compounds. Moreover, the selected compounds can generally be ionized using ESI and APCI modes with positive and negative polarity. The test mix can be used under formic acid or ammonium hydroxide conditions and with methanol or acetonitrile as an organic modifier. Performance monitoring with the enhanced mix is demonstrated with respect to ionization and mass measurement, as well as changes in gradient profile, flow rate, buffer pH, and ionic strength.
authors.affiliation: ArQule, Inc., Woburn, Massachusetts 01801, USA.
authors.forename: Shu
authors.initials: S
authors.lastname: Li
authors.forename: Lesline
authors.initials: L
authors.lastname: Julien
authors.forename: Peter
authors.initials: P
authors.lastname: Tidswell
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Goetzinger
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006863:Hydrogen-Ion Concentration; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000032:analysis*; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D013997:Time Factors
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents