Structural characterization of octreotide impurities by on-line electrochemistry-tandem mass spectrometry

Abstract

Octreotide, an octapeptide derivative of natural somatostatin, is widely used in the treatment of the secretion of gastrointestinal cancers, pituitary tumors, and acromegaly. To prolong the drug release, octreotide is extensively encapsulated with poly (D, L-lactic-co-glycolic acid) (PLGA) microspheres. While peptide impurities may be generated during fabrication of peptide-loaded microspheres and drug delivery processes, making the identification of peptide impurities a challenging task. For structural characterization of octreotide impurities, a new method based on mass spectrometry coupled with electrochemistry (EC-MS) was developed in this study. An electrospray ionization source with a grounded needle design was chosen as the coupling interface between electrochemistry and mass spectrometry, which simplifies instrument configuration and thus operation. Without any special sample preparation and any chemical reduction agents, disulfide bond in peptides was cleaved rapidly. The de novo sequencing octreotide and three acylated octreotides were easily obtained with followed tandem mass spectrometry. The results demonstrate that this method is suitable for fast evaluation and characterization of peptide containing disulfide bonds.