title: Applications of HILIC for targeted and non-targeted LC/MS analyses in drug discovery.
abstract: RP-HPLC has largely been the analytical method of choice in the pharmaceutical industry for many years because of the poor aqueous solubility and hydrophobicity of most small molecule drug candidates. RP-HPLC coupled to MS has provided an excellent analytical tool for qualitatively and quantitatively determining levels of drug molecules or drug metabolites for studies such as purity assessment and pharmacokinetic profiling. Quantitation of endogenous metabolites is an emerging field in drug discovery, gaining popularity for evaluating pharmacokinetic-pharmacodynamic relationships and targeting activity and efficacy. While RP-HPLC-MS is suitable for a range of applications, many endogenous molecules, especially those found in urine, are small polar compounds that do not retain well by RP-HPLC. This has made hydrophilic interaction LC (HILIC) an attractive alternative and useful approach to polar molecule analysis. Additionally, because HILIC is routinely used with traditional RP organic solvents such as ACN and methanol, it can be easily coupled to MS. This paper will review selected examples from the current literature as well as discuss some new applications from the author's own laboratory focusing on the applicability of HILIC to quantitative and qualitative profiling of endogenous metabolites in drug discovery.
authors.affiliation: Department of Bioanalytical and Discovery Analytical Science, Bristol-Myers Squibb Co., Princeton, NJ 08543-5400, USA. joelle.onorato@bms.com
authors.forename: Joelle M
authors.initials: JM
authors.lastname: Onorato
authors.forename: Robert
authors.initials: R
authors.lastname: Langish
authors.forename: Aouatef
authors.initials: A
authors.lastname: Bellamine
authors.forename: Petia
authors.initials: P
authors.lastname: Shipkova
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D055808:Drug Discovery; D013058:Mass Spectrometry / Q000379:methods*; D010599:Pharmacokinetics