Liquid Chromatography-High Resolution Mass Spectrometry for Peptide Drug Quality Control
Journal Title: The AAPS Journal - Year 2015, Vol 17, Issue 3
Abstract
A liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed using three peptide drugs: salmon calcitonin, bivalirudin, and exenatide as model systems to assess the suitability of this approach for monitoring peptide drug product quality. Calcitonin and its related impurities displayed linear responses over the range from 0.1 to 10 μM (R2 values for calcitonin salmon, Glu14-calcitonin, and acetyl-calcitonin were 0.995, 0.996, and 0.993, respectively). Intra-assay precision in terms of relative standard deviation (%RSD) was less than 10% at all tested concentrations. The accuracy of the method was greater than 85% as measured by spiking 0.1, 0.3, and 1% of Glu14-calcitonin and acetyl-calcitonin into a stock calcitonin solution. Limits of detection for calcitonin, Glu14-calcitonin, and acetyl-calcitonin were 0.02, 0.03, and 0.04 μM, respectively, indicating that an impurity present at less than 0.1% (0.1 μM) of the drug product API concentration (107 μM) could be detected. Method validation studies analyzing bivalirudin and exenatide drug products exhibited similar results to calcitonin salmon in regard to high selectivity, sensitivity, precision, and linearity. Added benefits of using LC-HRMS-based methods are the ability to also determine amino acid composition, confirm peptide sequence, and quantify impurities, even when they are co-eluting, within a single experiment. LC-HRMS represents a promising approach for the quality control of peptides including the measurement of any peptide-related impurities. While the development work performed here is focus on peptide drug products, the principles could be adapted to peptide drug substance.
Authors and Affiliations
Kui Zeng, Ilan Geerlof-Vidavisky, Ashley Gucinski, Xiaohui Jiang, Michael T. Boyne, II
Keywords
Related Articles
- EP ID EP680950
- DOI 10.1208/s12248-015-9730-z
- Views 62
- Downloads 0
Receptor-targeted gene delivery viafolate-conjugated polyethylenimine
A novel synthetic gene transfer vector was evaluated for tumor cell-specific targeted gene delivery. The folate receptor is a tumor marker overexpressed in more than 90% of ovarian carcinomas and large percentages of oth...
Biodegradable Microparticles Loaded with Doxorubicin and CpG ODN for In Situ Immunization Against Cancer
In situ immunization is based on the concept that it is possible to break immune tolerance by inducing tumor cell death in situ in a manner that provides antigen-presenting cells such as dendritic cells (DCs) with a wide...
Physiologically Based Pharmacokinetic Modelling of Drug Penetration Across the Blood–Brain Barrier—Towards a Mechanistic IVIVE-Based Approach
Predicting the penetration of drugs across the human blood–brain barrier (BBB) is a significant challenge during their development. A variety of in vitro systems representing the BBB have been described, but the...
Simulations of the Nonlinear Dose Dependence for Substrates of Influx and Efflux Transporters in the Human Intestine
The purpose of this study was to develop simulation and modeling methods for the evaluation of pharmacokinetics when intestinal influx and efflux transporters are involved in gastrointestinal absorption. The advanced com...
Statistics on BCS Classification of Generic Drug Products Approved Between 2000 and 2011 in the USA
The Biopharmaceutics Classification system (BCS) classifies drug substances based on aqueous solubility and intestinal permeability. The objective of this study was to use the World Health Organization Model List of Esse...