title: Modify on the fly: triple quad to high resolution in support of a dermal clinical study requiring an ultra low LLOQ.
abstract: BACKGROUND
  FTIH studies can be challenging due to the varying dosing regimens and rapid data delivery. Chemists are asked to provide ultra-low limits of quantitation to provide an understanding of patient efficacy and safety in order to progress drug development. In a recent dermal study it became necessary to reduce the LLOQ of a small molecule drug from 50 to 1 pg/ml due to reductions in the dose and surface area of drug application.
  
  
  METHODS
  The 50-fold increase in assay sensitivity necessitated the use of a high-resolution mass spectrometer (LC-HRMS) to separate matrix interferences observed when using a unit resolution triple quadrupole MS.
  
  
  CONCLUSIONS
  A sensitive, robust assay was validated to support of a FTIH study using a LC-HRMS.
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Chester L
authors.initials: CL
authors.lastname: Bowen
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kehler
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Boram
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Lee
authors.initials: L
authors.lastname: Abberley
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Mathew
authors.initials: M
authors.lastname: Szapacs
authors.affiliation: Bioanalytical Science & Toxicokinetics, DMPK, Platform Technology & Science, GlaxoSmithKline Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Evans
mesh_terms: D001774:Blood Chemical Analysis / Q000379:methods*; D002853:Chromatography, Liquid; D064368:Healthy Volunteers; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012867:Skin; D054852:Small Molecule Libraries / Q000032:analysis* / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D054852:Small Molecule Libraries
keywords: cross validation; first-time-in-human study; high-resolution MS; transdermal delivery