[125I]‐ and [14C]‐labelling of the long‐acting insulin derivative NN304

LysϵB29 Tetradecanoyl des(B30) human insulin, Novo Nordisk code no NN304, is a long-acting human insulin derivative that differs from human insulin by being more than 98% albumin bound in plasma. The syntheses of [125I]TyrA14 Nϵ-LysϵB29 Tetradecanoyl des (B30) human insulin ([125I]NN304) and LysϵB29 [I-14C]-Tetradecanoyl des (B30) human insulin ([14C]NN304) used for absorption, distribution, metabolism and excretion (ADME) studies are described. NN304 was radio-iodinated using the lactoperoxidase/hydrogen peroxide method, and the product was isolated using RP-HPLC. Radio-peptide mapping confirmed the [125I] labelling position at Tyrosine 14 in the A-chain. The radio-chemical yield was 30% with a radiochemical purity of >98%. [14C]NN304 was synthesised in two steps starting from 1-[14C] myristic acid and subsequently purified by HPLC. The overall radiochemical yield was 15% with a radiochemical purity >98%. Copyright © 2000 John Wiley & Sons, Ltd.