Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid-phase extraction and gas chromatography/mass spectrometry

Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented.     

Improved synthesis of the A-G ring segment of brevetoxin B

An efficient synthesis of the A-G ring segment 2, a key intermediate for the total synthesis of brevetoxin B (1), was achieved in 37 steps and 5.0% overall yield. The intramolecular allylation of the O,S-acetal 22, prepared from the ABC ring segment 15 and the FG ring segment 17, was carried out using AgOTf as a Lewis acid to give the desired compound 23, predominantly. Ring-closing metathesis of 23 with the Grubbs catalyst 12 afforded the heptacyclic ether 25. Selective hydrogenation of the E ring olefin of 25 was performed by diimide reduction to afford 2.     

The lifespan of solutions to nonlinear systems of a high-dimensional wave equation

In this work we study the lifespan of solutions to a p-q   system in the higher-dimensional case n?4.$n?4.$ A suitable local existence curve in the p-q   plane is found. The curve characterizes the local solutions in Sobolev space H^s$H^s$ with s?0.$s?0.$ Further, some lower and upper bounds of the lifespan of classical solutions are found too. This work is an extension of work [Geometric Optics and Related Topics, Progress in Nonlinear Differential Equations and their Applications, vol. 32, Birkhäuser, Basel, 1997, pp. 117–140], where a suitable global existence small data curve is studied. In the subcritical case, we give almost precise results for the lower bounds of the lifespan by using a suitable weighted Strichartz estimate for the higher-dimensional wave equation.     

Application of biphasic reaction procedure using ferric chloride dissolved in an imidazolium salt and benzotrifluoride (FeIm-BTF procedure) to aza-Prins cyclization reaction

Aza-Prins cyclization reaction of N-tosyl-3-butenylamine with aliphatic and aromatic aldehydes was performed using a combination of FeCl₃ and 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF₆) or 1-butyl-3-methylimidazolium tetrachloroferrate (BmimFeCl₄) in benzotrifluoride (BTF). The desired N-tosyl-4-chloro-2-substituted piperidines were obtained from aliphatic aldehydes in comparable yields to those for the previously reported reactions in which FeCl₃ was used in CH₂Cl₂. On the other hand, significant progress for the piperidine synthesis from aromatic aldehydes has been achieved, particularly when BmimFeCl₄ was used with FeCl₃ in BTF.     

Anti-biofouling properties of polymers with a carboxybetaine moiety

The resistance of random copolymers of BMA and CMB against biofouling was evaluated. The amount of proteins adsorbed onto the CMB copolymers was smaller than that onto other polymers (non-ionic polymers and copolymers of ordinary ionic monomers and BMA) and decreased with an increase in the content of CMB residues. Furthermore, there was a dramatic decrease in the number of cells (platelets and fibroblasts) that adhered to the CMB copolymers compared with that to other polymers. In contrast with this, CMB copolymers were slightly perturbative to both complement and coagulation systems. However, the overall results suggest that zwitterionic moieties are effective for making polymer materials biocompatible due to their excellent anti-biofouling property.