CPC A61K 49/108 (2013.01) [A61K 9/0019 (2013.01); A61K 31/28 (2013.01); A61K 49/106 (2013.01); C07D 257/00 (2013.01)] | 2 Claims |
1. A method of preparation of an MRI contrast agent which comprises:
(a) providing a liquid pharmaceutical solution which comprises a lanthanide metal complex free from excess lanthanide and M, where M is a metal ion impurity chosen from calcium, magnesium and zinc, or mixtures thereof, wherein said solution is prepared by a method comprising:
(i) complexing a chelator comprising said metal impurity M with an excess of said lanthanide metal in a solvent, to give a first solution of said lanthanide metal complex containing excess lanthanide ions and M;
(ii) removing the excess lanthanide ions and M from the first solution of step (i) by contacting said solution one or more times with a scavenger resin in pharmaceutically acceptable cationic organic salt form, whereby the excess lanthanide and M are complexed to said resin, wherein said resin comprises cationic meglumine counter ion;
(iii) separating the scavenger resin from the first solution of step (ii), to give a second solution which comprises said lanthanide metal complex free from excess lanthanide and M;
(b) optionally diluting the liquid pharmaceutical solution from step (a) with a biocompatible carrier to generate a formulation;
(c) dispensing the formulation from step (b) into pharmaceutically acceptable containers or syringes to give dispensed containers or syringes;
(d) either carrying out steps (a)-(c) under aseptic manufacturing conditions, or terminal sterilization of the dispensed containers or syringes from step (c), to give the MRI contrast agent in said pharmaceutically acceptable containers or syringes in a form suitable for mammalian administration; and
wherein said contrast agent comprises less than 10 ppm of M.
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