High performance liquid chromatography/electrospray tandem mass spectrometry for phenothiazines with heavy side chains in whole blood

Eleven phenothiazine derivatives with heavy side chains contained in human whole blood have been analyzed by high-performance liquid chromatography (HPLC)/electrospray (ES) tandem mass spectrometry (MS). All compounds gave the base peaks due to [M + 1](+) by HPLC/ES single MS. The product ions formed from each quasi-molecular ion by HPLC/ES tandem MS showed the base peaks due to side chains liberated. The mass chromatography of HPLC/ES tandem MS showed much higher sensitivity than that of HPLC/ES single MS for phenothiazines spiked to whole blood. Therefore, regression equations, detection limits, recovery rates and reproducibility were studied for thiethylperazine, clospirazine and flupentixol spiked to human whole blood by means of mass chromatography of HPLC/ES tandem MS. The three compounds showed good linearity in the range of 2-40 ng/mL with a detection limit of about 0.5 ng/mL. Recoveries of the three compounds spiked to whole blood (2 and 8 ng added to 1 mL whole blood) were 43.4-72.5 %; the coefficients of intraday and interday variations were 3.7-9.3 and 12.6-17.9 %, respectively. Thiethylperazine, clospirazine and flupentixol in whole blood could actually be determined with sufficient sensitivity 3 and 6 h after oral administration of 5-10 mg of each compound in a volunteer.     

Copolymerization of carbon disulfide and N-(β-cyanoethyl)ethylenimine

It was found that carbon disulfide copolymerizes with N-(β-cyanoethyl) ethylenimine by using water as a catalyst. The copolymerization was conducted in detail by using water as a catalyst in the temperature range between 0 and 50°C with various initial concentrations of carbon disulfide and N-(β-cyanoethyl)ethylenimine in the absence of solvent. The copolymer obtained was always composed of the two monomers: 1:1 ratio, independent of the initial concentration of the monomers. The copolymer was white solid material soluble in dimethyl sulfoxide, insoluble in other usual organic solvents and decomposed at 155°C. Spectroscopic analysis of the copolymer combined with the results of elemental analysis indicates that the copolymer had the following structure:      

Ethyl(methyl)dioxirane as an efficient reagent for the oxidation of nucleoside phosphites into phosphates under nonbasic anhydrous conditions

A convenient method for the oxidation of nucleoside phosphites into phosphates under nonbasic and nonaqueous conditions using commercially available ethyl(methyl)dioxirane has been developed. This oxidation is effective with both N-protected and N-unprotected strategies.     

Comparison of sonic spray lonization with atmospheric pressure chemical lonization as an interface of liquid chromatography-mass spectrometry for the analysis of some local anesthetics

Summary Sonic spray ionization (SSI) was compared with atmospheric pressure chemical ionization (APCI) as an interface for liquid chromatography (LC)-mass spectrometry (MS) for the analysis of some local anesthetics. Peaks at [M+H]⁺ constituted the base peaks for all compounds by both SSI and APCI, except for prilocaine. The sensitivities by SSI for tetracaine, benzoxinate, dibucaine, bupivacaine and mepivacaine were 4–16 times higher than those by APCI; those by SSI for procaine and lidocaine were equivalent to those by APCI. Only for prilocaine was the sensitivity by SSI two times lower than that by APCI. In view of the higher sensitivities obtained for many local anesthetics by SSI, we established a detailed procedure for the assay of these drugs in human plasma and urine by LC-MS with SSI in combination with a diol-bonded silica gel HPLC column that enabled direct injection of crude biological samples without complicated pretreatment. The recoveries, sensitivities, accuracies and precisions were found satisfactory to quantitate them at their therapeutic levels.     

Isolation of two new coumarin glycosides from Notopterygium forbesii and evaluation of a Chinese crude drug, qiang-huo, the underground parts of N. incisum and N. forbesii, by high-performance liquid chromatography

From the ether extract of the underground part of Notopterygium forbesii, two new coumarin glycosides, bergaptol-O-beta-D-glucopyranoside and 6'-O-trans-feruloylnodakenin, were isolated along with known compounds including seven furanocoumarins, two dihydrofuranocoumarins, a sterol glucoside and two phenolic compounds. Analysis of their contents by high-performance liquid chromatography (HPLC) revealed that the underground part of N. forbesii contained large amounts of p-hydroxphenethyl anisate (0.7%), bergaptol glucoside (0.2%), nodakenin (2%) and 6'-O-trans-feruloylnodakenin (0.7%) and a lesser amount of notopterol (0.08%), while that of N. incisum contained a large amount of notopterol (1.2%) and less amounts of the others. The characteristic difference in chemical composition between the two species enabled us to identify the respective botanical sources of a Chinese crude drug, Qiang-huo derived from N. incisum and N. forbesii by HPLC.     

Application of emissionless infrared diffuse reflectance spectrometry for following reactions of adsorbed alcohols on an alumina catalyst

IR spectra of adsorbed alcohols on alumina were measured under the reaction conditions at elevated temperatures. The transient response of IR absorption intensity indicates that alkoxides are reactive adsorbed species but carboxylates are not. The rate constants of surface reactions were calculated from the transient response.

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Epimerization of diastereomeric alpha-amino nitriles to single stereoisomers in the solid state

[reaction: see text] A diastereomeric mixture of the alpha-amino nitrile prepared by the Strecker reaction of benzaldehyde, (1S,2R)-1-aminoindan-2-ol, and cyanotrimethylsilane thermally epimerizes in the solid state to give a single diastereomer with an (S)-configuration at the alpha position to the nitrile moiety. This shows a sharp contrast to the reaction conducted in DMSO at room temperature, which gives a 1:1 mixture of (S)- and (R)-isomers. Several other alpha-amino nitriles also epimerize in the solid-state toward single diastereomers.     

Field survey of Glycyrrhiza plants in Central Asia (3). Chemical characterization of G. glabra collected in Uzbekistan

The chemical characteristics of Glycyrrhiza glabra L. were investigated at a habitat in Uzbekistan. HPLC analysis of the underground parts indicated that glycyrrhizin contents varied from 3.3 to 6.1% of dry weight, and that glabridin, a species-specific flavonoid for G. glabra, was detected in all underground samples (0.08-0.35% of dry weight). HPLC analysis of the leaves indicated that G. glabra plants collected in the present study could be divided into two types, RT-type and IQ-type, according to their major flavonol glycosides, rutin or isoquercitrin, respectively.     

Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions

The EC (Enzyme Commission) numbers represent a hierarchical classification of enzymatic reactions, but they are also commonly utilized as identifiers of enzymes or enzyme genes in the analysis of complete genomes. This duality of the EC numbers makes it possible to link the genomic repertoire of enzyme genes to the chemical repertoire of metabolic pathways, the process called metabolic reconstruction. Unfortunately, there are numerous reactions known to be present in various pathways, but they will never get EC numbers because the EC number assignment requires published articles on full characterization of enzymes. Here we report a computerized method to automatically assign the EC numbers up to the sub-subclasses, i.e., without the fourth serial number for substrate specificity, given pairs of substrates and products. The method is based on a new classification scheme of enzymatic reactions, named the RC (reaction classification) number. Each reaction in the current dataset of the EC numbers is first decomposed into reactant pairs. Each pair is then structurally aligned to identify the reaction center, the matched region, and the difference region. The RC number represents the conversion patterns of atom types in these three regions. We examined the correspondence between computationally assigned RC numbers and manually assigned EC numbers by the jackknife cross-validation test and found that the EC sub-subclasses could be assigned with the accuracy of about 90%. Furthermore, we examined the correlation with genomic information as represented by the KEGG ortholog clusters (OC) and confirmed that the RC numbers are correlated not only with elementary reaction mechanisms but also with protein families.