title: [(14) C]-AZD1152 drug substance manufacture: challenges of an IV-infusion dosed human mass balance study in patients.
abstract: [(14) C]-AZD1152 (barasertib) drug substance was prepared in order to support a hADME study that was to be dosed as an intravenous infusion to patients with acute myeloid leukaemia. A long patient recruitment time (1-2 years) was expected, and because of its limited stability several batches of [(14) C]-AZD1152 drug substance needed to be prepared in order to maintain a supply of [(14) C]-AZD1152 in the clinic over this period. A method was developed to purify the [(14) C]-AZD1152 to a GMP-like standard at high specific activity to provide material for each of these batches. This approach to the delivery of the drug substance was successful in supplying the study with radiolabelled drug for over 1 year until all patients had been recruited.
authors.affiliation: AstraZeneca UK Ltd., Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: Nick
authors.identifier: 0000-0002-9025-7015
authors.initials: N
authors.lastname: Bushby
authors.affiliation: AstraZeneca UK Ltd., Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Bergin
authors.affiliation: AstraZeneca UK Ltd., Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK.
authors.forename: John
authors.initials: J
authors.lastname: Harding
mesh_terms: D002250:Carbon Radioisotopes / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D007262:Infusions, Intravenous; D010755:Organophosphates / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics
chemical_list: C520647:2-((3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1H-pyrazol-3-yl)amino)quinazolin-7-yl)oxy)propyl)(ethyl)amino)ethyl dihydrogen phosphate; D002250:Carbon Radioisotopes; D010755:Organophosphates; D011799:Quinazolines
keywords: AZD1152; cGMP; hADME