Determination of traces of natural brassinosteroids as dansylaminophenylboronates by liquid chromatography with fluorimetric detection

A microanalytical method for the determination of traces of natural brassinosteroids as their dansylaminophenylboronates by liquid chromatography with fluorimetric detection is described. The boronates are easily prepared by the reaction of brassinosteroids with dansylaminophenylboronic acid (DABA), which was newly synthesized as a precolumn fluorogenic reagent for brassinosteroids. The potential of the method is demonstrated by the separation of a standard brassinosteroid mixture and the analysis of a biologically active fraction sample obtained from an extract of Zea mays L. pollen. The detection limit of the DABA derivative was found to be 25 pg for brassinolide, which is superior to that of the phenanthreneboronate derivative.     

Preparation and certification of JAC river water reference material for trace element analysis

 The Japan Society for Analytical Chemistry has recently issued a river water-certified reference material (CRM) for use in the ultratrace analysis of elements in fresh water. The river water CRM consists of a set of two (natural and spiked) 500-ml samples. The natural water is certified for Pb, Cr, As, Cu, Fe, Mn, Zn, B and Al at their sub-μg/l levels, while the spiked water is intended for use in the regulatory analysis of tap water and fresh water. Key words River water · Trace element analysis · Regulatory analysis · Reference materials     

Asymmetric total syntheses of (+)-mycoepoxydiene and related natural product (-)-1893A: application of one-pot ring-opening/cross/ring-closing metathesis to construct their 9-oxabicyclo[4.2.1]nona-2,4-diene skeleton

The total syntheses of (+)-mycoepoxydiene and (-)-1893A have been completed. The present synthetic strategy features the use of one-pot ring-opening/cross metathesis (ROM/CM) followed by a ring-closing metathesis (RCM) reaction, allowing for the concise construction of the 9-oxabicyclo[4.2.1]nona-2,4-diene framework from a 7-oxabicyclo[2.2.1]hept-2-ene derivative and 1,3-butadiene. The sequential metathesis product was converted into (+)-mycoepoxydiene through the oxidative rearrangement of a furfuryl alcohol to a pyranone, thereby establishing its absolute stereochemistry. From the common intermediate, a structurally related natural product (-)-1893A was also synthesized via the vinylogous aldol reaction.     

Determination of optimal formulation for extrusion granulation by compression test of wet kneaded mass

The purpose of this study is to propose the application of a compression test to the determination of an optimal formulation for extrusion granulation. The electric current during extrusion was measured and the characteristics of the wet kneaded mass in the compression test were analyzed under various operating conditions, with different types of extruders and several formulations of kneaded mass. It was found that addition of a binder (HPC-L) to pharmaceutical powders lowered the load of a high-compressing type extruder, since the binder reduced the friction among the wet mass during extrusion. Also, the support stress was found to be proportional to the compression pressure without a binder, although an inflection point appeared on the support stress curve when a binder was present. This inflection point suggested large water retention of the wet kneaded mass, at which the medium of pressure was changed from a discontinuous solid powder to a continuous liquid, and large water retention contributed to the low friction of the wet mass. The friction of the wet kneaded mass and the aptitude of the formulation for extrusion were understood by using the compression test. The compression test is a very useful procedure at the first stage of a formulation study.     

Reaction of azole condensed quinoxaline N-oxides with acetic anhydride

The reaction of 7-chlorotetrazolo[1,5-α]quinoxaline 5-oxide 6a with acetic anhydride gave 7-chloro-5-(7-chlorotetrazolo[1,5-α]quinoxalin-4-yl)-4,5-dihydro-4-oxotetrazolo[1,5-α]quinoxaline 7a , while the reaction of 7-chloro-1,2,4-triazolo[4,3-α]quinoxaline 5-oxide 6b with acetic anhydride afforded 7-chloro-5-(7-chloro-1,2,4-triazolo[4,3-α]quinoxalin-4-yl)-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 7b and 7-chloro-4,5-dihydro-4-oxo-1,2,4-triazolo[4,3-α]quinoxaline 8b . The reaction of compound 6a or 6b with acetic anhydride/acetic acid provided 7-chloro-4,5-dihydro-4-oxo-tetrazolo[1,5-α]quinoxaline 8a or compound 8b , respectively.     

Multi-turn time-of-flight mass spectrometers with electrostatic sectors

The mass resolution of a time-of-flight (TOF) mass spectrometer is directly proportional to its total flight pathlength. Multi-turn or multi-passage ion optical geometries are necessary to obtain fight distances of sufficient length within reasonable size limitations. We have investigated ion optics for a multi-turn TOF mass spectrometer with electrostatic sectors. The concept of 'perfect' focusing conditions is introduced. Furthermore, a new type of multi-turn TOF mass spectrometer, the MULTUM Linear plus, was developed. It consists of four cylindrical electric sectors and 28 electric quadrupole lenses. It has a vacuum chamber 60 x 70 x 20 cm in size. Mass resolution is demonstrated to increase according to the number of ion cycles. A mass resolution of 350 000 (m/z = 28, FWHM) was achieved after 501.5 cycles. The MULTUM Linear plus analyzer is not simple, however; 28 electric quadrupole lenses are used. In order to reduce the number of ion optical parts, an improved multi-turn TOF mass spectrometer, the MULTUM II, consisting of only four toroidal electric sectors, was also developed. The possibility of tandem mass spectrometric applications using multi-turn TOF mass spectrometers is also discussed.     

Effect of surface covering of lactose carrier particles on dry powder inhalation properties of salbutamol sulfate

The effect of the surface covering of lactose carrier particles on the dry powder inhalation properties of salbutamol sulfate was investigated. Lactose carrier surfaces were covered with sucrose tristearate (J-1803F) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer). In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with various particle surface conditions prepared by surface covering. These powder mixtures were aerosolized by a Jethaler), and the in vitro inhalation properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with uncovered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface covering lactose carrier were significantly different, showing that the in vitro inhalation properties of salbutamol sulfate were improved. In vitro inhalation properties increased with the percentage of J-1803F added. Using this surface covering system would thus be valuable for increasing the inhalation properties of dry powder inhalation with lactose carrier particles.     

Influence of storage humidity on the in vitro inhalation properties of salbutamol sulfate dry powder with surface covered lactose carrier

The influence of storage humidity on the in vitro inhalation properties of salbutamol sulfate dry powder with surface covered lactose carrier was investigated. In the present study, drug/carrier powder mixtures were prepared consisting of micronized salbutamol sulfate and lactose carriers with different particle surface conditions prepared by surface covering. Lactose carrier surfaces were covered with vegetable magnesium stearate (Mg-St-V) by a high-speed elliptical-rotor-type powder mixer (Theta-Composer). These powder mixtures were aerosolized by a Jethaler), and the in vitro inhalation properties of salbutamol sulfate were evaluated by a twin impinger. Compared with the powder mixed with uncovered lactose carrier, the in vitro inhalation properties of the powder mixture prepared using the surface covered lactose carrier were little decreased with increased in relative humidity (RH), showing that the in vitro inhalation properties of salbutamol sulfate were improved at high RH. Using this surface covering technique would thus be valuable for storage humidity of dry powder inhalation (DPI) with lactose carrier particles.     

Synthetic alpha-mannosyl ceramide as a potent stimulant for an NKT cell repertoire bearing the invariant Valpha19-Jalpha26 TCR alpha chain

A NKT cell repertoire is characterized by the expression of the Valpha19-Jalpha26 invariant TCR alpha chain (Valpha19 NKT cell). This repertoire, as well as a well-established Valpha14-Jalpha281 invariant TCR alpha(+) NKT cell subset (Valpha14 NKT cell), has been suggested to have important roles in the regulation of the immune system and, thus, is a major therapeutic target. Here, we attempted to find specific antigens for Valpha19 NKT cells. Valpha19 as well as Valpha14 NKT cells exhibited reactivity to alpha-galactosyl ceramide (alpha-GalCer). Thus, a series of monoglycosyl ceramides with an axially oriented glycosidic linkage between the sugar and ceramide moiety were synthesized and their antigenicity to Valpha19 NKT cells was determined by measuring their immune responses in culture with glycolipids. Comprehensive examinations revealed substantial antigenic activity for Valpha19 NKT cells by alpha-mannosyl ceramide.