Direct determination of benzamides in serum by column-switching high-performance liquid chromatography.

A column-switching high-performance liquid chromatographic method with fluorescence detection was developed for the simultaneous determination of four benzamide-type anti-psychotic drugs: sulpiride, tiapride, sultopride and metoclopramide in human serum. In this method, a TSKgel Super-ODS column was used as an analytical column, and a TSKgel G 2000SW was prepared as a pretreatment column. Under the optimized analytical conditions, four benzamide-type anti-psychotic drugs were eluted within 18 min. The detection limits (S/N = 3) for sulpiride, tiapride, sultopride and metoclopramide are 1 ng/ml, 4 ng/ml, 2 ng/ml and 0.5 ng/ml, respectively. Finally, the method was applied to the determination of sulpiride in human serum samples obtained after a single oral dose of sulpiride.     

Synthesis of 3-hydroxyindolin-2-one alkaloids, (±)-donaxaridine and (±)-convolutamydines A and E, through enolization-Claisen rearrangement of 2-allyloxyindolin-3-ones

Claisen rearrangement triggered by enolization of 2-allyloxyindolin-3-ones with DBU was performed in order to prepare 3-allyl-3-hydroxyindolin-2-ones. Total synthesis of 3-hydroxyindolin-2-one alkaloids, (±)-donaxaridine, as well as (±)-convolutamydines A and E, was achieved by transformation of the allyl moiety of 3-allyl-3-hydroxyindolin-2-ones.     

Evaluation of radioimmunoassay of the blood tobramycin level for the purpose of setting the dosage based on the clinical pharmacokinetic theory and a comparison of radioimmunoassay with other assay methods

With the purpose to use for therapeutic drug monitoring (TDM), blood concentrations of tobramycin (TOB) in each patient were measured by radioimmunoassay (RIA). A RIA kit of TOB (Clinical assay-Japan Travenol) was evaluated for precision and recovery, in that partial improvement of the method was made, in order to measure low level of TOB. The RIA was compared with high-performance-liquid-chromatography (HPLC), bioassay (BA) and 2 kinds of enzyme immunoassay (EIA) (EMIT and SLFIA). The RIA of TOB revealed high precision (1.8-2.4% in C.V.) and high reproducibility (5.0-6.9% in C.V.). It was found that this RIA kit can be used for measuring low level of serum TOB concentrations by a modification of the method. The total range of measurable blood level is from 0.1 to 16.0 micrograms/ml. The nearly one to one correspondence was observed between RIA and other 4 methods, when 154 samples obtained from 18 cases were measured. A representative case of TDM for TOB was demonstrated, in which predicted concentrations agreed fairly well with actual measured values at steady state. It was concluded that the RIA kit is useful for clinical application of TDM for the adequate dosage regimen of TOB. Modification of the method for rapid assay of a small number of samples will increase the clinical usefulness.     

Rapid ruthenium-catalyzed synthesis of pyranopyrandiones by reconstructive carbonylation of cyclopropenones involving C[bond]C bond cleavage

Pyranopyrandiones were prepared by a novel ruthenium-catalyzed carbonylative dimerization of cyclopropenones via C-C bond cleavage. For example, treatment of dipropylcyclopropenone with a catalytic amount of Ru3(CO)12 and NEt3 in THF under 15 atm of carbon monoxide at 140 degrees C for 20 h gave a novel functional monomer, 3,4,7,8-tetrapropylpyrano[6,5-e]pyran-2,6-dione, in an isolated yield of 81%. Unsymmetrically substituted pyranopyrandiones were also obtained by ruthenium-catalyzed carbonylative coupling of cyclopropenones with alkynes under similar reaction conditions.     

Tuning of luminescence spectra of neutral ruthenium(II) complexes by crystal waters

Neutral ruthenium(II) complexes [RuLL'(CN)2] (L, L' = bpy, dmb, dbb; bpy = 2,2'-bipyridine, dmb = 4,4'-dimethyl-2,2'-bipyridine, dbb = 4,4'-tert-butyl-2,2'-bipyridine) were prepared, and the luminescence characteristics of the complexes in the solid state were measured. The luminescence was tuned by crystal waters included in the crystals; for example, [Ru(dbb)2(CN)2] x 2H2O, [Ru(dbb)2(CN)2] x H2O, and [Ru(dbb)2(CN)2] emit luminescence at 640, 685, and 740 nm, respectively.     

New class of potent catalysts of O2.-dismutation. Mn(III) ortho-methoxyethylpyridyl- and di-ortho-methoxyethylimidazolylporphyrins

Three new Mn(III) porphyrin catalysts of O2.-dismutation (superoxide dismutase mimics), bearing ether oxygen atoms within their side chains, were synthesized and characterized: Mn(III) 5,10,15,20-tetrakis[N-(2-methoxyethyl)pyridinium-2-yl]porphyrin (MnTMOE-2-PyP(5+)), Mn(III)5,10,15,20-tetrakis[N-methyl-N'-(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTM,MOE-2-ImP(5+)) and Mn(III) 5,10,15,20-tetrakis[N,N'-di(2-methoxyethyl)imidazolium-2-yl]porphyrin (MnTDMOE-2-ImP(5+)). Their catalytic rate constants for O2.-dismutation (disproportionation) and the related metal-centered redox potentials vs. NHE are: log k(cat)= 8.04 (E(1/2)=+251 mV) for MnTMOE-2-PyP(5+), log k(cat)= 7.98 (E(1/2)=+356 mV) for MnTM,MOE-2-ImP(5+) and log k(cat)= 7.59 (E(1/2)=+365 mV) for MnTDMOE-2-ImP(5+). The new porphyrins were compared to the previously described SOD mimics Mn(III) 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)), Mn(III) 5,10,15,20-tetrakis(N-n-butylpyridinium-2-yl)porphyrin (MnTnBu-2-PyP(5+)) and Mn(III) 5,10,15,20-tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin (MnTDE-2-ImP(5+)). MnTMOE-2-PyP(5+) has side chains of the same length and the same E(1/2), as MnTnBu-2-PyP(5+)(k(cat)= 7.25, E(1/2)=+ 254 mV), yet it is 6-fold more potent a catalyst of O2.-dismutation , presumably due to the presence of the ether oxygen. The log k(cat)vs. E(1/2) relationship for all Mn porphyrin-based SOD mimics thus far studied is discussed. None of the new compounds were toxic to Escherichia coli in the concentration range studied (up to 30 microM), and protected SOD-deficient E. coli in a concentration-dependent manner. At 3 microM levels, the MnTDMOE-2-ImP(5+), bearing an oxygen atom within each of the eight side chains, was the most effective and offered much higher protection than MnTE-2-PyP(5+), while MnTDE-2-ImP(5+) was of very low efficacy.     

Wavelength effect on the photoinduced reaction of polymethylmethacrylate

Polymethylmethacrylate (PMMA) containing benzophenone (BP) was photo-irradiated with monochromatic radiation of wavelength 260–360 nm using the Okazaki Large Spec-trograph (OLS). On irradiation of PMMA films containing BP in air, the sensitized main-chain scission and photocrosslinking of PMMA took place simultaneously. These reactions are dependent on irradiation wavelength. The threshold wavelength for both reactions is found to be ca. 380 nm. The number of main-chain scission and amount of gel increased with the increase of BP concentration in PMMA. Photosensitized main-chain scission favors the irradiation of radiation at ca. 280 nm and photocrosslinking takes place efficiently with the exposure of 340 nm radiation. A possible mechanism for photosensitized reaction is proposed. © 1995 John Wiley & Sons, Inc.     

Analysis of phenothiazines in human body fluids using disk solid-phase extraction and liquid chromatography

Seven phenothiazine derivatives, perazine, perphenazine, prochlorperazine, propericiazine, thioproperazine, trifluoperazine, and flupentixol, have been found to be extractable from human plasma and urine samples using disk solid-phase extraction (SPE) with an Empore C18 cartridge. Human plasma and urine (1 mL each) containing the 7 phenothiazine derivatives were mixed with 2 mL of 0.1M NaOH and 7 mL distilled water and then poured into the disk SPE cartridges. The drugs were eluted with 1 mL chloroform- acetonitrile (8 + 2) and determined by liquid chromatography with ammonium formate/formic acid-acetonitrile gradient elution. The detection was performed by ultraviolet absorption at 250 nm. The separation of the 7 phenothiazine derivatives from each other and from impurities was generally satisfactory using a SymmetryShield RP8 column (150 x 2.1 mm id, 3.5 microm particle size). The recoveries of the 7 phenothiazine derivatives spiked into plasma and urine samples were 64.0-89.9% and 65.1-92.1%, respectively. Regression equations for the 7 phenothiazine derivatives showed excellent linearity, with detection limits of 0.021-0.30 microg/mL for plasma and 0.017-0.30 microg/mL for urine. The within-day and day-to-day coefficients of variation for both samples were commonly below 9.0 and 14.9%, respectively.     

Catalytic enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes catalyzed by well-defined chiral ru amido complexes

Well-defined chiral Ru amido complexes promoted asymmetric Michael addition of 1,3-dicarbonyl compounds including malonates, beta-keto esters, and 1,3-diketones to nitroalkenes to give the corresponding adducts with excellent ees and in excellent yields.