Insulin related compounds and identification

Identification of Lysine Misincorporation at Asparagine Position in Recombinant Insulin Analogs Produced in E. coli

“…The best known impurities of insulin and insulin analogs are desamido A21 and desamido B3 derivatives ( 6 ). Other related proteins of insulins identified during drug production or storage are: des-Thr-insulin which is an undesirable side-product, di-Arg B31-B32 -insulin, and Arg-insulin, which are intermediates during insulin production, N αB1 carbamoyl insulin, N αA1 carbamoyl insulin ( 7 – 9 ) acetylated lispro insulin ( 10 ), desPhe B1 -N-oxalyl-Val B2 insulin ( 11 ), desPhe B1 -, desPhe B1 -N-formyl-Val B2 - and pyroGlu B4 insulin ( 12 ), covalent insulin dimers ( 13 ), insulin fragments ( 14 ), misincorporated A9 (Ser → Asn) human insulin ( 14 ) and insulin with amino acid residues oxidized to 3,4-dihydroxyphenylalanine (DOPA) and 2-amino-3-(3,4-dioxocyclohexa-1,5-dien-1-yl) propanoic acid (DOCH) ( 15 ). Such impurities present in a protein substance and dosage forms cannot exceed acceptable amounts in order to meet the Pharmacopoeia requirements ( 16 ).…”