title: Advantages of atmospheric pressure photoionization mass spectrometry in support of drug discovery.
abstract: The performance of the atmospheric pressure photoionization (APPI) technique was evaluated against five sets of standards and drug-like compounds and compared to atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI). The APPI technique was first used to analyze a set of 86 drug standards with diverse structures and polarities with a 100% detection rate. More detailed studies were then performed for another three sets of both drug standards and proprietary drug candidates. All 60 test compounds in these three sets were detected by APPI with an overall higher ionization efficiency than either APCI or ESI. Most of the non-polar compounds in these three sets were not ionized by APCI or ESI. Analysis of a final set of 201 Wyeth proprietary drug candidates by APPI, APCI and ESI provided an additional comparison of the ionization techniques. The detection rates in positive ion mode were 94% for APPI, 84% for APCI, and 84% for ESI. Combining positive and negative ion mode detection, APPI detected 98% of the compounds, while APCI and ESI detected 91%, respectively. This analysis shows that APPI is a valuable tool for day-to-day usage in a pharmaceutical company setting because it is able to successfully ionize more compounds, with greater structural diversity, than the other two ionization techniques. Consequently, APPI could be considered a more universal ionization method, and therefore has great potential in high-throughput drug discovery especially for open access liquid chromatography/mass spectrometry (LC/MS) applications.
authors.affiliation: Discovery Analytical Chemistry, Chemical and Screening Sciences, Wyeth Research, CN 8000, Princeton, NJ 08543, USA. caiy1@wyeth.com
authors.forename: Yanxuan
authors.initials: Y
authors.lastname: Cai
authors.forename: David
authors.initials: D
authors.lastname: Kingery
authors.forename: Oliver
authors.initials: O
authors.lastname: McConnell
authors.forename: Alvin C
authors.initials: AC
authors.lastname: Bach
mesh_terms: D000818:Animals; D001272:Atmosphere; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D004345:Drug Industry; D006801:Humans; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations