Abstract: Provided are methods for preparing a biological sample for analysis for the presence of a virus, or an exosome or other extra-cellular vesicle, by matrix assisted laser desorption ionisation time of flight mass spectrometry (MALDI-ToF MS). The preparation involves mixing the sample with at least one cationic viral envelope/vesicle disruptor compound, or at least one disulphide reducing agent, or a combination thereof; and at least one mass spectrometry grade solvent. Also provided are methods for analysing a biological sample for the presence of a virus, or an exosome or other extra-cellular vesicle, using MALDI-ToF MS once prepared.