Comparison of Structurally Related Impurity Profiles in Teriparatide From Synthetic and Recombinant DNA Origin Using...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Science
• Biochemistry

Background:

• Teriparatide (TPT) is a key osteoporosis treatment.
• Generic drug development requires rigorous impurity profiling.
• Understanding TPT impurities is vital for regulatory assessment.

Purpose of the Study:

• To systematically characterize impurity profiles of TPT reference materials from diverse synthetic origins.
• To develop and validate a method for identifying and quantifying structurally related impurities in TPT.
• To inform regulatory evaluations of generic TPT drug products.

Main Methods:

• Liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) was employed.
• Analysis utilized electro-spray ionization (ESI) Orbitrap mass spectrometry.
• External standard methods and four quantitative scenarios were applied for accurate impurity quantification.

Main Results:

• Distinct impurity profiles were observed between chemically synthesized and recombinant TPT materials.
• Common impurities included one isomer and three oxidation products.
• Six unique amino acid deletion impurities were identified in chemically synthesized TPT, with eight novel impurities characterized overall.

Conclusions:

• A robust LC-HRMS method was established for TPT impurity profiling.
• Synthetic source-specific impurity monitoring is essential for TPT production.
• This characterization enhances the regulatory evaluation of generic peptide drugs.