Search for organic bioindicators in the solar system is a fundamental challenge for the space research community. If tremendous improvements have been achieved in detection, little or no research has been dedicated to extraction of the targets from the studied mineral matrices. Apart from thermodesorption, no extraction step was ever performed in situ within the context of biomarker detection experiments. This work presents an extraction protocol compatible with in situ space constraints. Two extraction methods, i.e., microwave-assisted extraction (MAE) and focused ultrasonic extraction (FUSE), were optimized with the aim of extracting molecules having an astrobiological interest (amino acids, nucleobases, polyaromatic carboxylic acids) and that are included in mineral matrices representative of the Martian soil. Higher efficiency was obtained with the FUSE method (20 kHz, amplitude 80%, pulse and relaxation 1 s each, for 10 min) with yields ranging from 30 to 95%. It was then applied on an Atacama Desert soil sample and Aguas Zarcas meteorite fragment. Both water-soluble and organic-soluble compounds present at trace levels were extracted using this short extraction time, and small amounts of sample and solvent compliant with in situ requirements (50 mg, 500 mu L). This unique FUSE/derivatization-GC-MS approach gave similar yields to usual 24 h hot water extraction and increased the recovery of the target molecules compared to the derivatization-GC-MS method already used for in situ space experiments by a factor from 2 to 8. The data highlighted the suitability of a focused ultrasonic method for the extraction of trace organic compounds from extraterrestrial samples.Read less <