Abstract：
Octreotide acetate, the active pharmaceutical ingredient in the long-acting release (LAR) drug product Sandostatin®, is a cyclic octapeptide that mimics the naturally occurring somatostatin peptide hormone. Modern NMR can be a robust analytical method to identify and quantify octreotide molecules. Previous 1H chemical shift assignments were mostly performed in organic solvents, and no assignments for heteronuclear 13C, 15N, and aromatic 1H nuclei are available. Here, using state-of-the-art 1D and 2D homo- and heteronuclear NMR experiments, octreotide was fully assigned, including water exchangeable amide protons, in aqueous buffer except for 13CO and 15NH of F1, 15NH of C2, and 15NζHζ of K5 that were not observed because of water exchange or conformational exchange. The solution NMR spectra were then directly compared with 1D 1H/13C/15N solid-state NMR (SSNMR) spectra showing the potential applicability of 13C/15N SSNMR for octreotide drug product characterization.
摘要：
醋酸奥曲肽,长效释放（LAR）药物产品Sandostatin®中的活性药物成分，是模拟天然存在的生长抑素肽激素的环状八肽。现代NMR可以是鉴定和定量奥曲肽分子的可靠分析方法。以前的1H化学位移分配大多在有机溶剂中进行，没有异核13C的分配，15N,和芳族1H核是可用的。这里,使用最先进的1D和2D同核和异核核磁共振实验，奥曲肽被完全分配，包括水可交换的酰胺质子，在水性缓冲液中，除了由于水交换或构象交换而未观察到的F1的13CO和15NH，C2的15NH和K5的15NζHζ。然后将溶液NMR光谱与1D1H/13C/15N固态NMR（SSNMR）光谱直接比较，显示13C/15NSSNMR用于奥曲肽药物产品表征的潜在适用性。
