Anionic Acid Labile Surfactants (AALS) are novel, acid cleavable detergents that are fully compatible with mass spectrometry analysis. At neutral pH, Anionic Acid Labile Surfactant II acts as a powerful detergent for use in sample preparation, protein solubilization, and cell lysis protocols. It is an alternative for SDS and other commonly used anionic detergents used in protein analysis. When experimental solutions are adjusted to a pH of 2.5 - 3 with trifluoroacetic acid (TFA) and incubated for 10 minutes, the acid labile surfactant is fully cleaved into small organic molecules that do not exhibit surfactant activity or interfere with mass spectrometry analysis. The detergent is compatible with ESI and MALDI mass spectrometry analysis.