P4 The Use of Desorption Electrospray Ionisation (DESI) Mass Spectrometry Imaging (MSI) for Direct Drug Analysis in Polymeric Implants

Elizabeth E Pierson , Merck Research Laboratories, Rahway, NJ
William P Forrest , Merck Research Laboratories, Rahway, NJ
Megan Mackey , Merck Research Laboratories, Rahway, NJ
Roy Helmy , Merck Research Laboratories, Rahway, NJ
Hernando J Olivos , Waters Corporation, Beverley, MA
Anthony J Midey , Waters Corporation, Beverley, MA
Michael A Batey , Waters Corporation, Manchester, United Kingdom
Bindesh Shrestha , Waters Corporation, Beverley, MA
Delivering a drug via polymeric implants provides extended and tunable release rates tailored to therapeutic need and, more importantly, leads to improved patient compliance [J. Arps, Med. Design Technol., July 2013]. Therapy development benefits from understanding the uniformity of drug distribution in the implant and how it changes as the implant ages. Applying mass spectrometry imaging (MSI) to an implant creates a spatial map of chemical species in the sample. Desorption Electrospray Ionization (DESI) directly samples and ionizes at atmospheric pressure for rapid analysis with essentially no sample preparation required. The ESI mechanism works well with Active Pharmaceutical Ingredients (APIs). Thus, DESI MSI of drug implants gives spatial distributions from a non-flat surface quickly with little preparation. Erodible polymeric implants containing a model API compound were directly analyzed using DESI MSI with a SYNAPT G2-Si ion mobility QToF MS. The two formulations differ in polymer identity and result in differences in API release rates. The distributions of the API in the implants were imaged both before and after exposure to release media, which causes the polymer matrix to degrade and API to release. No additional sample preparation was performed beyond anchoring the implants to a blank glass slide. DESI solvent mixtures were used to desorb and ionize the implant surfaces. The MSI data were acquired, processed, and analyzed using High Definition Imaging (HDI) software v1.4 with Mass Lynx v4.1 data acquisition.DESI MSI measured a mass spectrum (intensity vs. m/z) at each point (i.e., pixel) on a virtual “grid” superimposed on the analyzed implant. HDI software constructed the spatial distribution of each m/z peak on the implants and visualized their intensities across the imaged area. The chemical map was overlaid with an optical image of the implant to co-register the molecular distribution on it. Ions generated from DESI on blank, erodible polymer implants (no API) were mapped along various parts of the implant. Intact, drug-containing implants were then analyzed to map the distribution of the API on the implant surface. Radial cross sections were also imaged to measure API distribution on the implant interior. Typical adduct ions produced with ESI on drug APIs such as [M+H]+ and [M+Na]+ were readily observed by DESI. Drug-containing implants were exposed to release media to cause implant erosion and simulate aging. Analogous DESI MSI experiments were conducted to map the distribution on radial sections of the treated drug implant. Comparing the MS imaging data from the original implants and the two eroded implants showed the effect of the implant erosion on the drug distributions as well as the effect of polymer identity on release rate. An image correlation filter using a Pearson product-moment applied to the spatial distribution of API ions was employed to rank other detected ions based on spatial correlation in each pixel. Ions with the highest spatial correlation to the API distribution were determined using this method. We anticipate this DESI MSI workflow to be widely applicable to other drugs and utilized for understanding drug delivery implants.