Improvement of mechanical properties of orodispersible hyaluronic acid film by carboxymethyl cellulose addition.

Orodispersible films (ODF) were prepared with mixtures of hyaluronic acid (HA) and carboxymethyl cellulose (CMC), and the effect of CMC addition on the disintegration and mechanical properties of the composite films were examined. Low molecular weight HA (10 kDa) appeared more acceptable for ODF than high molecular weight HA (800 kDa) because of its rapid disintegration in the oral cavity. The composite films appeared similar to pullulan film with excellent transparency and surface smoothness. The disintegration time as well as mechanical properties of the films such as tensile strength and elongation at break were increased by the addition of CMC. Overall, the CMC addition, up to 35%, improved the mechanical properties of low molecular weight HA film within a proper range of disintegration time for ODF.

Impact of single and dual modifications on physicochemical properties of japonica and indica rice starches.

The japonica (JR) and indica (IR) rice starches were modified by acetylation, hydroxypropylation, cross-linking, and dual modification (cross-linked acetylation and cross-linked hydroxypropylation) and the effects of single and dual chemical modifications of JR and WR on the physicochemical properties were investigated. The JR had a greater substitution degree of acetyl or hydroxypropyl groups than IR. The dual-modified JR showed broader gelatinization temperature range than corresponding single-modified starches, but narrower it in IR. The dual-modified JR and IR showed higher pasting temperature and lower breakdown than their corresponding single-modified starches. The dual modification with JR and IR induced significant increase in gel hardness as compared to the corresponding unmodified and single-modified starches. The dual-modified JR had a greater hardness, gumminess, and chewiness than the dual-modified IR. The different impact of single and dual modification with JR and IR on the physicochemical properties could be due to the differences in the location and distribution of substituent groups on the starch molecules.

Profiling analysis of biogenic amines and their acidic metabolites in mouse brain tissue using gas chromatography-tandem mass spectrometry.

The profiling analysis of biogenic amines, including catecholamines and serotonin, and their metabolites in mouse brain tissue provides an important key to understanding their roles in the body and the possibility of simple and accurate diagnosis of neural diseases. A novel approach in the analysis of biogenic amines and their acidic metabolites in brain tissue using gas chromatography-tandem mass spectrometry (GC-MS/MS) is presented. Biogenic amines and their acidic metabolites in brain tissue were effectively separated using a mixed-cation-exchange solid-phase extraction (MCX-SPE) cartridge with a variation in the composition of the SPE elution solvents. A selective derivatization with hexamethyldisilazane (HMDS) and N-methyl-bis-heptafluorobutyramide (MBHFBA) was used to increase the detection sensitivity and to prevent the formation of any side-products. The identification and quantification of the target analytes were performed by gas chromatography triple quadrupole mass spectrometry (GC-MS/MS) using multiple ion reaction monitoring (MRM) mode. The overall recovery yields of the biogenic amines and their metabolites were above 87.5% at 10ng/g and 92.4% at 100ng/g of spiking concentration range. The isotopic-labeled internal standards were used for the precise quantification of bioamines and their metabolites. The calibration curves for the biogenic amines and their metabolites obtained through GC-MS/MS were linear (r(2)>0.995) over the concentration range of 1 (2 or 3)-200ng/mL. The present method was reproducible (relative standard deviation range 0.6-9.3%) and accurate (range 85.4-107.9%), with LLOQs of 0.71-3.69ng/mL. The developed method was successfully applied to the determination and quantification of bioamines and their metabolites in rat brain tissue samples.

GC-MS/MS method for the quantification of α-cedrene in rat plasma and its pharmacokinetic application.

α-Cedrene is a pharmacologically active ingredient isolated from the essential oil of cedar. A selective and sensitive GC-MS/MS method was developed for the quantification of α-cedrene in rat plasma for the first time. α-Cedrene was extracted from rat plasma using ethyl acetate at neutral pH. The analytes were determined in selective reaction monitoring mode using MS/MS: m/z 204.3→119.0 for α-cedrene and m/z 146.0→111.0 for 1,4-dichlorobenzene (internal standard). The standard curve was linear (r(2) ≥ 0.995) over the concentration ranges of 5-800 ng/mL. The lower limit of quantification was 5 ng/mL using 50 µL of rat plasma. The coefficient of variation and relative error for intra- and interassays at four quality control levels were 3.1-13.9% and -4.0-2.6%, respectively. The stability of processing (freeze-thaw, long-term storage at -80°C, and short-term storage at room temperature) and chromatography (reinjection) was shown to be of insignificant effect. The present method was applied successfully to the pharmacokinetic study of α-cedrene after its intravenous (10 mg/kg) and oral (25 mg/kg) administration in male Sprague-Dawley rats.

Comprehensive profiling analysis of bioamines and their acidic metabolites in human urine by gas chromatography/mass spectrometry combined with selective derivatization.

A comprehensive analytical method was developed for the profiling of biogenic amines in human urine using GC/MS in SIM mode. Biogenic amines and their acidic metabolites were converted into their volatile O-trimethylsilyl/N-heptafluorobutyryl (OTMS/-NHFBA) derivatives for GC/MS analysis. Dual hexamethyldisilazane (HMDS)/-N-methyl-bis-heptafluorobutyramide (MBHFBA) derivatizations have been shown to be quite effective, with high derivatization yields and the absence of side products for primary biogenic amines. In this study, selective derivatization conditions by HMDS/MBHFBA were optimized in terms of the reagent amount, reaction temperature and reaction time period. The highest derivatization reaction yield was obtained at 40°C for 10min for OTMS derivatization and 80°C for 5min for N-HFBA derivatization. The use of MCX SPE cartridges with different SPE elution solvents was effective for the pre-concentration and selective cleanup of the biogenic amines and their acidic metabolites in human urine. The selection of appropriate ions in SIM mode provided reliable quantification and identification and a reduction in background effects. The established method was validated in terms of linearity, limits of detection (LOD), limits of quantification (LOQ), precision, and accuracy. The present method was linear (r(2)>0.996), reproducible (relative standard deviation range 1.1-6.9%), and accurate (range 87.9-111.9%), with LOQs of 0.17-17.84ng/mL. The biogenic amine profiling of human urine was successfully accomplished by GC/MS in SIM mode combined with selective HMDS/MBHFBA derivatization and MCX SPE cleanup.

One-pot synthesis of 2-pyridones via chemo- and regioselective tandem Blaise reaction of nitriles with propiolates.

The Blaise reaction intermediate, generated in situ from Reformatsky reagent and nitrile, reacted with propiolates in a chemo- and regioselective manner to afford 2-pyridone derivatives in good to excellent yields.

Structural determination of sildenafil and its analogues in dietary supplements by fast-atom bombardment collision-induced dissociation tandem mass spectrometry.

Sildenafil and its analogues, which are used as illegal additives in several dietary supplements, were isolated by liquid-liquid extraction and column chromatography and analyzed by fast-atom bombardment mass spectrometry (FAB-MS). Structures of sildenafil and its derivatives were elucidated by FAB-tandem mass spectrometry (MS/MS) with exact mass measurement in the positive-ion mode. To find structurally diagnostic ions for the sildenafil analogues, authentic sildenafil was preferentially analyzed by high-energy collision-induced dissociation (CID)-MS/MS. The CID-MS/MS spectra of [M+H](+) precursor ions resulted in the formation of numerous characteristic ions via a series of dissociative processes. The product ions formed by CID provided important information on the modification of the piperazine ring, the phenylsulfonyl group and the pyrazolopyrimidine moiety of sildenafil. By interpreting their MS/MS spectra, the chemical structures of sildenafil analogues isolated from dietary supplements could be elucidated and fragmentation patterns were proposed. To clearly identify the sidenafil derivatives in dietary supplements, some of the derivatives such as acetildenafil, homosildenafil and hydroxyhomosildenafil which are not commercially available were synthesized and compared with their MS/MS spectra. In addition, high-resolution mass measurements were conducted to obtain the elemental compositions of sildenafil and its analogues.

Structural determination of monoacylglycerols extracted from marine sponge by fast atom bombardment tandem mass spectrometry.

Five new monoacylglycerols (MAGs) were isolated from the marine sponge Stelletta sp. by reversed-phase high-performance liquid chromatography and analyzed by positive ion fast atom bombardment mass spectrometry (FAB-MS). FAB mass spectra of these compounds produced abundant sodium-adducted molecules [M+Na]+ from a mixture of 3-nitrobenzyl alcohol and sodium iodide. The structural elucidation of these sponge MAGs was carried out by FAB tandem mass spectrometry (MS/MS). To find diagnostic ions for the characterization of the MAGs, authentic MAGs were initially analyzed by collision-induced dissociation (CID) MS/MS. The CID MS/MS of [M+Na]+ precursor ions resulted in the formation of numerous characteristic product ions via a series of dissociative processes. The product ions formed by charge-remote fragmentation (CRF) provided important information for the characterization of acyl chains substituted at the glycerol backbone, and product ions at m/z 84, 97, 113 and 139 were diagnostic for the sodiated glycerol backbone. On the basis of these fragmentation patterns, the structures of five MAGs extracted from marine sponge were elucidated. In addition, high-resolution mass measurement was performed to obtain the elemental compositions of the MAGs.