'Space weathering' is the term applied to the darkening and reddening of planetary surface materials with time, along with the changes to the depths of absorption bands in their optical spectra. It has been invoked to explain the mismatched spectra of lunar rocks and regolith, and between those of asteroids and meteorites. The formation of nanophase iron particles on regolith grains as a result of micrometeorite impacts or irradiation by the solar wind has been proposed as the main cause of the change in the optical properties. But laboratory simulations have not revealed the presence of these particles, although nano-second-pulse laser irradiation did reproduce the optical changes. Here we report observations by transmission electron microscopy of olivine samples subjected to pulse laser irradiation. We find within the amorphous vapour-deposited rims of olivine grains nanophase iron particles similar to those observed in the rims of space-weathered lunar regolith grains. Reduction by hydrogen atoms implanted by the solar wind is therefore not necessary to form the particles. Moreover, the results support the idea that ordinary chondrites came from S-type asteroids, and thereby provides some constraints on the surface exposure ages of those asteroids.

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A study of the pharmacokinetics of (14)C-labeled acetaminophen (AAP) was performed in healthy Japanese subjects receiving an oral microdose of the drug. After separation by high-performance liquid chromatography (HPLC), the levels of AAP and its metabolites in the pooled plasma specimens were quantified using accelerator mass spectrometry (AMS). The total body clearance (CL(tot))/bioavailability (F) of AAP was within the variation in the reported values at therapeutic doses, indicating the linearity of AAP pharmacokinetics. AAP-glucuronide (Glu) and AAP-4-O-sulfate satisfied the criteria of safety testing of drug metabolites. AMS could detect AAP-Cys, the active metabolite of AAP conjugated with cysteine, in the urine. Probenecid prolonged the systemic elimination of total radioactivity and caused a marked decrease in AAP-Glu levels in plasma. Probenecid likely inhibited the glucuronidation of AAP and the renal elimination of AAP-4-O-sulfate. Microdosing of (14)C-labeled drug followed by AMS is a powerful tool that can be used in the early phase of drug development for pharmacokinetic analysis of drugs and their metabolites and for detecting the formation of active metabolites in humans.

A technique utilizing simultaneous intravenous microdosing of (14)C-labeled drug with oral dosing of non-labeled drug for measurement of absolute bioavailability was evaluated using R-142086 in male dogs. Plasma concentrations of R-142086 were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and those of (14)C-R-142086 were measured by accelerator mass spectrometry (AMS). The absence of metabolites in the plasma and urine was confirmed by a single radioactive peak of the parent compound in the chromatogram after intravenous microdosing of (14)C-R-142086 (1.5 microg/kg). Although plasma concentrations of R-142086 determined by LC-MS/MS were approximately 20% higher than those of (14)C-R-142086 as determined by AMS, there was excellent correlation (r=0.994) between both concentrations after intravenous dosing of (14)C-R-142086 (0.3 mg/kg). The oral bioavailability of R-142086 at 1 mg/kg obtained by simultaneous intravenous microdosing of (14)C-R-142086 was 16.1%, this being slightly higher than the value (12.5%) obtained by separate intravenous dosing of R-142086 (0.3 mg/kg). In conclusion, on utilizing simultaneous intravenous microdosing of (14)C-labeled drug in conjunction with AMS analysis, absolute bioavailability could be approximately measured in dogs, but without total accuracy. Bioavailability in humans may possibly be approximately measured at an earlier stage and at a lower cost.

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