Capsule-Type Hydrothermal Extraction-Coupled NanoESI-MS/MS for Analysis of Uranium Isotope in Sub-milligram Lunar Regolith Samples

Abstract Uranium concentration and isotopic data from returned extraterrestrial materials provide constraints on planetary differentiation, thermal evolution, and chronological frameworks. However, the extreme paucity of such specimens demands analytical methodologies capable of analysis at ultratrace sample amounts. Herein, we report an integrated workflow coupling capsule-type hydrothermal extraction (CTHE) with nanoelectrospray ionization tandem mass spectrometry (nanoESI-MS/MS) for the determination of uranium isotope in sub-milligram lunar regolith. Leveraging the hydrostatic pressure balancing strategy, sub-milligram samples were hydrothermally digested within a polytetrafluoroethylene micro-capsule using HF/HNO3 at high-temperature and high-pressure conditions. Following controlled elimination of residual acids, uranium was converted to the [UO2(NO3)3]− complex and analyzed by nanoESI-MS/MS in the negative ion mode via selective reaction monitoring of the characteristic transitions m/z 456.0 → 410.0 (238U) and m/z 453.0 → 407.0 (235U). The optimized method affords a limit of detection of 0.63 μg/L, a linear dynamic range spanning 0.01–2.00 mg/L (R2 > 0.99), a sample consumption as low as 0.1 mg, and spike recoveries of 92.4–97.4% with relative standard deviations (RSDs) < 4% (n = 3). Application of the CTHE-nanoESI-MS/MS method to Chang’e-5 lunar regolith afforded a uranium concentration of 1.44 ± 0.06 μg/g and a 235U/238U ratio of 0.007198 ± 0.000102 (RSD = 1.42%, δ = −8.13‰ relative to the certified natural uranium value). Notably, this approach reduces sample consumption by two orders of magnitude relative to conventional hydrothermal digestion combined ICP–MS detection methods. This methodology establishes an analytical paradigm for uranium isotope geochemistry in sample-limited materials.