Deamidation analysis of therapeutic drugs using matrix-assisted laser desorption ionization mass spectrometry and a novel algorithm QuanDA†

A robust deamidation quantification method, called QuanDA, was developed to quantify the spontaneous nonenzymatic deamidation of peptides based on the isotopic distribution change of peptides in matrix-assisted laser desorption ionization (MALDI) mass spectra and non-negative least squares calculation. The predictive model of QuanDA using theoretical spectra of pure un-deamidated and deamidated peptides for a series of simulated partial deamidated peptides is satisfying, with a coefficient of determination (R²) and root mean squared error (RMSE) of 0.9914 and 0.03356, respectively. It was applicable in cases where there is a lack of reference standards of un-deamidated and deamidated peptides. The only requirements were the chemical formulae of un-deamidated and deamidated peptides for isotopic pattern calculation. QuanDA provided a rapid, low-cost and easily accessible method for deamidation analysis in therapeutic drugs.