Toshinari Oh-hara

Comprehensive quantitative and qualitative liquid chromatography–radioisotope–mass spectrometry analysis for safety testing of tolbutamide metabolites without standard samples

Liquid chromatography-radioisotope-mass spectrometry (LC-RI-MS) analysis was used to determine the structures of 12 (four previously unknown) (14) C-tolbutamide (TB) metabolites in rat biological samples (plasma, urine, bile, feces, and microsomes). The four novel metabolites are ω-carboxy TB, hydroxyl TB (HTB)-O-glucuronide, TB-ortho or meta-glutathion, and tolylsulphoaminocarbo-glutathion. In rat plasma, after oral administration of (14) C-TB at therapeutic dose (1 mg/kg) and microdose (1.67 µg/kg), the total RI and six metabolites [HTB, carboxy TB (CTB), M1: desbutyl TB, M2: ω-hydroxyl TB, M3: α-hydroxyl TB, and M4: ω-1-hydroxyl TB] were quantified by LC-RI-MS. The plasma concentrations were calculated using their response factors (MS-RI intensity ratio) without standard samples, and the area under the curve (AUC) of plasma concentration per time for evaluation of Safety Testing of Drug Metabolites (MIST) was calculated using the ratio of TB metabolites AUC/total RI AUC. The ratios were as follows: TB 94.5% and HTB 2.5% for the microdose (1.67 µg/kg) and TB 95.6%, HTB 0.96%, CTB 0.065%, M1 0.62%, M2 0.0035%, M3 0.077%, and M4 0.015% for the therapeutic dose (1 mg/kg). These values were less than 10% of the MIST criteria.

Highly coherent tunable mid-infrared frequency comb pumped by supercontinuum at 1 µm

We report a tunable mid-infrared frequency comb working at 184 MHz, which is based on difference frequency generation in a periodically poled Mg-doped stoichiometric lithium tantalate (PPMgSLT) crystal pumped by high-power supercontinuum pulses. Supercontinuum pulses from two fibers with different dispersion properties were examined. With a photonic crystal fiber (PCF) having normal dispersion properties, a tunable wavelength range of 2.9–4.7 µm was achieved. With another PCF having zero dispersion at 1040 nm, a maximum power of 1.34 mW was observed at 3.9 µm. The high coherence of the pulses generated with this scheme was verified experimentally, and a fringe visibility of 0.90 was observed.