Determination of ondansetron and its hydroxy metabolites in human serum using solid-phase extraction and liquid chromatography/positive ion electrospray tandem mass spectrometry

Ondansetron and its hydroxylated metabolites were determined in human serum using solid-phase extraction (SPE) and liquid chromatography/positive ion electrospray tandem mass spectrometry. Pyrimethamine was used as the internal standard. The analytes were eluted from the SPE cartridge using 2 x 1 ml of methanol containing 0.5% triethylamine, evaporated under vacuum and the residue was reconstituted in the mobile phase. The liquid chromatographic separation was achieved on a silica column using a mobile phase of aqueous 20 mM ammonium acetate (pH 4.7)-acetonitrile (85 : 15, v/v) at a flow-rate of 0.4 ml min(-1). The method was linear over the range 1-500 ng ml(-1) for ondansetron and each of the metabolites in human serum. The intra-day accuracy was better than 9.1% and the precision was <10.3%; the inter-day accuracy was better than 9.5% and the precision was <12.6%. The limit of detection was 250 pg ml(-1) based on a signal-to-noise ratio of 3. The absolute recovery from serum for all analytes was >90%.     

The separation of tellurium and selenium by polyurethane foam sorbents

Tellurium and selenium can be sorbed from hydrochloric acid and hydrobromic acid solution by both polyether and polyester-based polyurethane foam. Although some acid is needed, the substitution of sodium chloride or sodium bromide increases the extraction significantly. Tellurium is extracted rapidly with > 99% sorbed in 2 min from 1.0/5.0M and 2.0/4.0M hydrochloric acid/sodium bromide. Selenium can also be sorbed quantitatively but much more slowly so that a separation is possible based on the relative rates of extraction. The capacity of polyether foam is 3% by weight of tellurium.     

HPLC separations of meropenem and selected pharmaceuticals using a polar endcapped octadecylsilane narrow bore column

Summary Stability indicating high performance liquid chromatography methods have been developed for the assay of meropenem in combination with either dopamine (A), aminophylline (B), metoclopramide (C) or ranitidine (D) in intravenous fluid mixtures. Separations B, C and D were performed on a polar endcapped ODS column (150×2 mm) with aqueous, pH 3.0—acetonitrile (89∶11, 88∶12, and 92∶8) eluent and detection at 270, 290, 317 nm respectively. Meropenem was linear over the concentration ranges 126.88–507.50, 131.25–525, and 131.25–525 gmg mL⁻¹. Aminophylline, metoclopramide and ranitidine were linear over the concentration ranges 13–52, 37.5–150, and 25–100 μg mL⁻¹. Separation A was performed on a conventional ODS column (150×2.1 mm) with aqueous, pH 3.0—acetonitrile (85∶15) eluent and detection at 280 nm. Meropenem and dopamine were linear in the 61.25–245 and 10–40 μg mL⁻¹ ranges, respectively. Accuracy and precision for all methods were 0.20–3.30% and 0.10–1.58%, respectively. Accelerated stability studies have been carried out on each drug by exposure to acid, base, H₂O₂, and heat for different time periods.     

An interlaboratory capillary zone electrophoresis-UV study of various monoclonal antibodies,instruments, and ε-aminocaproic acid lots

Capillary zone electrophoresis ultraviolet (CZE-UV) has become increasingly popular for the charge heterogeneity determination of mAbs and vaccines. The ε-aminocaproic acid (eACA) CZE-UV method has been used as a rapid platform method. However, in the last years, several issues have been observed, for example, loss in electrophoretic resolution or baseline drifts. Evaluating the role of eACA on the reported issues, various laboratories were requested to provide their routinely used eACA CZE-UV methods, and background electrolyte compositions. Although every laboratory claimed to use the He et al. eACA CZE-UV method, most methods actually deviate from He's. Subsequently, a detailed interlaboratory study was designed wherein two commercially available mAbs (Waters’ Mass Check Standard mAb [pI 7] and NISTmAb [pI 9]) were provided to each laboratory, along with two detailed eACA CZE-UV protocols for a short-end, high-speed, and a long-end, high-resolution method. Ten laboratories participated each using their own instruments, and commodities, showing excellence method performance (relative standard deviations [RSDs] of percent time-corrected main peak areas from 0.2% to 1.9%, and RSDs of migration times from 0.7% to 1.8% [n = 50 per laboratory], analysis times in some cases as short as 2.5 min). This study clarified that eACA is not the main reason for the abovementioned variations.     

An evaluation of trapping compounds used for determining14CO2 by liquid scintillation counting

Four commonly used trapping agents for scintillation counting of¹⁴CO₂ (Hyamine, Primene, ethanolamine and β-phenylethylamine) were assessed under identical conditions, the progress of trapping being measured directly by pressure changes and by liquid scintillation counting. It was found that quantitative absorption required considerably longer periods of time than those previously reported and that absorption at low¹⁴CO₂ pressures was very slow. The effects of pressure and stirring rate were also studied.     

The molecular structure of 1,1-dimethyl-3-phenylpyrazolium-5-oxide

The molecular structure of 1,1-dimethyl-3-phenylpyrazolium-5-oxide has been determined by a single crystal x-ray diffraction study. The crystals are monoclinic, space group P2₁/a, with unit cell dimensions a = 12.630 (5) Å, b = 6.644 (1) Å, c = 12.486 (5) Å, β = 99.17 (2)°. The final R value was 0.049 for 2930 reflections. The bond lengths and angles suggest that a significant contribution to the structure is made by a resonance form in which one of the ring bonds does not exist. No close intermolecular approaches were found.     

The synthesis of “stretched-out” analogs of lumazine, 6,7-dimethyllumazine and 2-amino-5,6,7,8-tetrahydro-6,7-dimethyl-4-pteridinone

The synthesis of pyrazino[2,3-g]quinazolin-2,4-(1H,3H)dione ( 4 ) and its 7,8-dimethyl derivative ( 5 ), as linear benzo-separated lumazines, is reported. Also described is the preparation of 2-amino-6,7,8,9-tetrahydro-7,8-dimethylpyrazino[2,3-g]quinazolin-4-one ( 6 ), as a linear benzo-separated analog of a synthetic cofactor for phenylalanine hydroxylase. All of the syntheses began with ethyl 2,4,5-triaminobenzoate ( 8 ) and proceeded through the appropriate derivatives of ethyl 6-aminoquinoxaline-7-carboxylate ( 9, 10 , and 11 ) which were subsequently ring closed to 4, 5 , and 6 .     

Pharmazeutische Pr?parate

Ohne Zusammenfassung     

Reactivity of bis(2,2,5,5-tetramethyl-2,5-disila-1-azacyclopent-1-yl)tin with CO(2), OCS, and CS(2) and comparison to that of bis[bis(trimethylsilyl)amido]tin

The heterocumulenes carbon dioxide (CO(2)), carbonyl sulfide (OCS), and carbon disulfide (CS(2)) were treated with bis(2,2,5,5-tetramethyl-2,5-disila-1-azacyclopent-1-yl)tin {[(CH(2))Me(2)Si](2)N}(2)Sn, an analogue of the well-studied bis[bis(trimethylsilyl)amido]tin species [(Me(3)Si)(2)N](2)Sn, to yield an unexpectedly diverse product slate. Reaction of {[(CH(2))Me(2)Si](2)N}(2)Sn with CO(2) resulted in the formation of 2,2,5,5-tetramethyl-2,5-disila-1-oxacyclopentane, along with Sn(4)(μ(4)-O){μ(2)-O(2)CN[SiMe(2)(CH(2))(2)]}(4)(μ(2)-N═C═O)(2) as the primary organometallic Sn-containing product. The reaction of {[(CH(2))Me(2)Si](2)N}(2)Sn with CS(2) led to formal reduction of CS(2) to [CS(2)](2-), yielding [{[(CH(2))Me(2)Si](2)N}(2)Sn](2)CS(2){[(CH(2))Me(2)Si](2)N}(2)Sn, in which the [CS(2)](2-) is coordinated through C and S to two tin centers. The product [{[(CH(2))Me(2)Si](2)N}(2)Sn](2)CS(2){[(CH(2))Me(2)Si](2)N}(2)Sn also contains a novel 4-membered Sn-Sn-C-S ring, and exhibits a further bonding interaction through sulfur to a third Sn atom. Reaction of OCS with {[(CH(2))Me(2)Si](2)N}(2)Sn resulted in an insoluble polymeric material. In a comparison reaction, [(Me(3)Si)(2)N](2)Sn was treated with OCS to yield Sn(4)(μ(4)-O)(μ(2)-OSiMe(3))(5)(η(1)-N═C═S). A combination of NMR and IR spectroscopy, mass spectrometry, and single crystal X-ray diffraction were used to characterize the products of each reaction. The oxygen atoms in the final products come from the facile cleavage of either CO(2) or OCS, depending on the reacting carbon dichalogenide.     

A versatile synthesis of functionalised 2-aminoquinolines by mercury controlled cyclisation of 2-vinylphenylthioureas

4-(4-Hydroxyphenyl)-2-phenylamino-1,8-naphthyridine was prepared via cyclisation of N-phenyl-N′-3-(4-hydroxyphenethen-1-yl)pyridin-2-ylthiourea in the presence of mercuric oxide. Derivatives of 4-methyl-2-aminoquinolines were prepared in a similar manner from 2-vinylphenylthioureas.