Solid State NMR Analysis

The focus of this proposal is on the characterization and quantitation of Ventassa„µ (Patiromer), which is a drug product that was approved in 2015 for the treatment of hyperkalemia. The active ingredient in Patiromer is a polymeric anion that is composed of three different monomeric species. The monomeric species include 2-fluoroprop-2-eneoate, with crosslinking groups diethenylbenzene and octa-1,7-diene, with the primary species being 2-fluoroprop-2-enoate. The relative ratio of the species is purported to be 91% for the 2-fluoroprop-2-enoate, with 9% being the crosslinking groups, per the package insert. The specific goal of this project is to be able to quantify the peaks representing the carboxylate (or carboxylic acid equivalent) and aromatic carbons in the Patiromer that are present in the sample using solid-state NMR spectroscopy. The first step in the proposal is to be able to evaluate and quantify the carboxylate and aromatic carbons so that the relative ratio of those two species can be calculated and determined. The second step is to compare several different lots of Patiromer such that the relative ratio of the species will be determined. This proposal will be divided into three different parts. The first part will be an introduction to quantitative solid-state NMR spectroscopy, specifically focused on the ability to quantify different functional groups and some of the caveats that must be avoided in order to obtain quantitative data. The second part will focus on the quantitation of Veltassa, including the specific NMR parameters that need to be determined in order to obtain quantitative data for the different species. The last section will focus on the background of the investigator, including experience in performing quantitative 13C solid-state NMR spectroscopy.