Direct analysis of proteins and peptides in complex matrices is of significant importance for biological, medicinal and toxicological studies.

Paper spray (PS) has demonstrated a promising future for direct mass spectrometric analysis. In the process of PS, paper substrate has been demonstrated as a crucial factor in determining the final performance of PS-MS, and therefore much attention is paid to modification of paper substrate. In this review, we systematically introduce the development of paper substrate for PS. Various commercial and modified papers are comprehensively reviewed, and much effort is focused on some physical and chemical approaches for modification of paper substrate. The application of modified paper substrates to biological sample analyses is discussed. The future promising directions of paper substrate for PS are highlighted.

A soft metal salt assisted electrospray ionization mass spectrometry has been developed to characterize directly GAP polymers through the complexing effect of anions from metal salts with glycidyl azide polymers (GAP) in a negative ion mode.