Abstract: A process for purifying a compound of formula 1, includes the following steps: a) adding an acid to an aqueous solution of the compound of formula 1, including salts and hydrates thereof so as to obtain a slurry having a pH?3; and b) filtering the slurry and at least one time washing the obtained precipitate with a liquid comprising water; and c) dissolving the precipitate obtained in step b) in water to obtain an aqueous solution; and d) filtering of the solution obtained in step c) over a nanofiltration membrane having a Molecular Weight Cut Off in the range from 150 to 500 and wherein optionally, between step c) and step d) the pH of the aqueous solution is adjusted to a pH value in the pH range as specified by the manufacturer of the nanofiltration membrane. A process for preparing a gadolinium complex of the purified compound of formula 1 is also disclosed. This gadolinium complex can be used for making a pharmaceutical composition as a contrast agent for magnetic resonance imaging.

Abstract: A process for purifying a compound of formula 1, includes the following steps: a) adding an acid to an aqueous solution of the compound of formula 1, including salts and hydrates thereof so as to obtain a slurry having a pH?3; and b) filtering the slurry and at least one time washing the obtained precipitate with a liquid comprising water; and c) dissolving the precipitate obtained in step b) in water to obtain an aqueous solution; and d) filtering of the solution obtained in step c) over a nanofiltration membrane having a Molecular Weight Cut Off in the range from 150 to 500 and wherein optionally, between step c) and step d) the pH of the aqueous solution is adjusted to a pH value in the pH range as specified by the manufacturer of the nanofiltration membrane. A process for preparing a gadolinium complex of the purified compound of formula 1 is also disclosed. This gadolinium complex can be used for making a pharmaceutical composition as a contrast agent for magnetic resonance imaging.

Abstract: A process for producing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) including salts and hydrates thereof of general formula (I) from the respective cyclen. The process involves the use of cationic- and anionic exchange resins and solvent treatments to remove the organic and inorganic contaminants. Any cations present in the raw DOTA or other contaminants resulting from the reaction of cyclen are largely reduced in early stages of the process allowing to obtain good yields of DOTA in a purified grade and in an easier and reliable way. The process is useful for the production of DOTA, of macrocyclic compounds including metal ions complexes thereof and of compositions including the macrocyclic compounds that can be used as contrast agents for magnetic resonance imaging.

Abstract: A process for producing a complex of a lanthanide or similar compound with a macrocyclic ligand, wherein the ratio of macrocyclic ligand in free form in relation to the lanthanide or similar compound is equal or more than 0.002% mol/mol, includes the steps of a) measuring the moisture content in a sample of the macrocyclic ligand; and b) mixing an amount G of the lanthanide with an amount X3 of the macrocyclic ligand with the proviso that X3=LG+Lf+M, wherein LG is the amount of macrocyclic ligand necessary for complexing the amount G of lanthanide or similar compound, Lf is an excess amount of the macrocyclic ligand, and M is the amount of moisture present in the amount X3 of the macrocyclic ligand.

Abstract: A process for producing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) including salts and hydrates thereof of general formula (I) from the respective cyclen. The process involves the use of cationic- and anionic exchange resins and solvent treatments to remove the organic and inorganic contaminants. Any cations present in the raw DOTA or other contaminants resulting from the reaction of cyclen are largely reduced in early stages of the process allowing to obtain good yields of DOTA in a purified grade and in an easier and reliable way. The process is useful for the production of DOTA, of macrocyclic compounds including metal ions complexes thereof and of compositions including the macrocyclic compounds that can be used as contrast agents for magnetic resonance imaging.