METHOD OF PREPARING FORMULATIONS OF LANTHANIDE METAL COMPLEXES OF MACROCYCLIC CHELATES

摘要

A method of preparation of a liquid pharmaceutical formulation comprising a metal complex of a lanthanide metal with a macrocyclic chelate and an amount of uncomplexed chelate in the final pharmaceutical formulation of between 0.002 and 0.4 mol/mol% of the metal complex, the method comprising the following steps: i) mixing a solution of uncomplexed chelate with a lanthanide metal or compound thereof and with a base to obtain complexation of the lanthanide metal with the chelate, in such amounts that not all the chelate is complexed; ii) contacting the solution one or more times with an amount of an anion exchange resin, the amount of the resin is between 1 and 50 times the amount of uncomplexed chelate, the amount of resin is expressed as equivalents and the amount of uncomplexed chelate is expressed as moles; iii) separating the solution from the resin.