A reliable and accurate laser ablation multi-collector inductively coupled plasma mass spectrometry (LA-MC-ICP-MS) method was developed for analysis of inhomogeneous samples containing uranium particles or aggregates of various enrichments. For the method development, a mixed solid standard was prepared using 1% and 3% 235U enriched certified reference materials. After screening and localization of the particles of interest, the U isotopic composition was analysed for a 5-µm sample spot determining accurately and precisely the various constituents. Besides the LA-MC-ICP-MS, the standard was also measured by large-geometry secondary ion mass spectrometry (LG-SIMS) for additional verification.