title: Semiempirical Rules To Determine Drug Sensitivity and Ionization Efficiency in Secondary Ion Mass Spectrometry Using a Model Tissue Sample.
abstract: There is an increasing need in the pharmaceutical industry to reduce drug failure at late stage and thus reduce the cost of developing a new medicine. Since most drug targets are intracellular, this requires a better understanding of the drug disposition within a cell. Secondary ion mass spectrometry has been identified as a potentially important technique to do this, as it is label-free and allows imaging in 3D with subcellular resolution and recent studies have shown promise for amiodarone. An important analytical parameter is sensitivity, and we measure this in a bovine liver homogenate reference sample for 20 drugs representing important class types relevant to the pharmaceutical industry. We also measure the sensitivity for pure drug and show, for the first time, that the secondary ion mass spectrometry (SIMS) positive ionization efficiency for small molecules is a simple power-law relationship to the log P value. This discovery will be important for advancing the understanding of the SIMS ionization process in small molecules that has, until now, been elusive. This simple relationship is found to hold true for drug doped in the bovine liver homogenate reference sample, except for fluticasone, nicardipine, and sorafenib which suffer from severe matrix suppression. This relationship provides a simple semiempirical method to determine drug sensitivity for positive secondary ions. Furthermore, we show, on chosen models, how the use of different solvents during sample preparation can affect the ionization of analytes.
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Vorng
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Kotowska
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Melissa K
authors.initials: MK
authors.lastname: Passarelli
authors.affiliation: GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: West
authors.affiliation: GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Marshall
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Havelund
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Seah
authors.affiliation: GlaxoSmithKline , Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, United Kingdom.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Dollery
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Paulina D
authors.initials: PD
authors.lastname: Rakowska
authors.affiliation: National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), National Physical Laboratory , Hampton Road, Teddington, Middlesex TW11 0LW, United Kingdom.
authors.forename: Ian S
authors.initials: IS
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D002417:Cattle; D004345:Drug Industry; D007477:Ions / Q000737:chemistry; D008099:Liver / Q000737:chemistry*; D015394:Molecular Structure; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D018629:Spectrometry, Mass, Secondary Ion
chemical_list: D007477:Ions; D004364:Pharmaceutical Preparations