Tetsuo Hayase

Comparison of molecular mobility in the glassy state between amorphous indomethacin and salicin based on spin-lattice relaxation times

Purpose.The purpose of the current study was to evaluate the molecular mobility of amorphous indomethacin and salicin in the relaxed glassy state based on spin-lattice relaxation times (T1c) and to clarify the effects of molecular mobility on their physical stability.Methods.Pulverized glassy amorphous indomethacin and salicin samples were completely relaxed, and the T1c values were investigated using solid-state 13C-nuclear magnetic resonance (NMR) at temperatures below the glass transition temperature (Tg). All NMR spectra were obtained using the T1c measurement method combined with variable-amplitude cross-polarization, the Torchia method, and total sideband suppression method.Results.The T1c value of amorphous indomethacin indicated that 73% of carbons were in a state of monodispersive relaxation, suggesting that the amorphous state was relatively homogeneous and restricted, particularly in backbone carbons. On the other hand, 92% of carbons of amorphous salicin exhibited both fast and slow biphasic relaxation. Individual structures of the salicin molecules behaved heterogeneously, and thus the entire molecule showed relatively fast local as well as slow mobility.Conclusions.At temperatures below Tg, amorphous salicin had relatively greater molecular mobility than amorphous indomethacin. This difference in the molecular mobility of the two compounds is correlated with their crystallization behavior. Solid-state 13C NMR provides valuable information on the physical stability of amorphous pharmaceuticals.

A new sensitive determination method of estradiol in plasma using peroxyoxalate ester chemiluminescence combined with an HPLC system.

A new sensitive determination method of estradiol in a plasma sample using peroxyoxalate ester chemiluminescence was developed. Estradiol, which was extracted by liquid-liquid extraction using ethyl acetate from plasma, was derivatized with dansyl-chloride (DNS-Cl) and separated by reverse-phase HPLC. The performance of four oxalates, bis(trichlorophenyl)oxalate (TCPO), bis(2,4-dinitrophenyl)oxalate (DNPO), bis(pentafluorophenyl)oxalate (PFPO), and bis[4-nitro-2-(3,6, 9-trioxadecyloxycarbonyl)phenyl] oxalate (TDPO), were evaluated using the static system, and DNPO was found to have the most sensitive and stable chemiluminescence at a H(2)O(2) concentration of 30 mM. HPLC-chemiluminescence system using DNPO for the determination of estradiol was established. The detection limit of dansylated-estradiol (DNS-E2) was 15 fmol (4 pg) in the standard solution and 44 fmol (12 pg) in the rat plasma sample at S/N = 3.