Quantitative determination of phenothiazine derivatives in human plasma using monolithic silica solid-phase extraction tips and gas chromatography-mass spectrometry

Solid-phase extraction (SPE) using micropipette tips is a useful technique to prepare samples prior to mass spectrometry. However, most commercial SPE tips have loading capacities that are insufficient for quantitative determination. In this paper, we describe a rapid method for quantitative microanalysis of five phenothiazine derivatives, chlorpromazine, levomepromazine, promazine, promethazine and trimeprazine, using a recently introduced C(18) monolithic silica SPE tip, the MonoTip C(18), for extraction from human plasma. The drugs could be extracted within 5 min from 0.1-mL plasma samples, eluted with methanol, and the eluate injected directly into a gas chromatograph prior to mass spectrometry analysis. Only 0.7 mL of solvent was required for each step of the extraction process. The recoveries of the five phenothiazines spiked into plasma were 91-95% and the limits of quantification for each drug were between 0.25 and 2.0 ng/0.1 mL. The maximum intra- and inter-day coefficient of variation was 11%. The validated method was successfully used to quantify the plasma concentration of levemepromazine in a human subject after oral administration of the drug. This new method is expected to have wide applications as a pretreatment for the rapid, quantitative determination of drug concentrations in plasma samples.     

Automated on-line in-tube solid-phase microextraction coupled with HPLC/MS/MS for the determination of butyrophenone derivatives in human plasma

This paper describes a fully automated on-line method combining in-tube solid-phase microextraction (SPME) in which sample clean-up and enrichment are conducted through an open tubular fused-silica capillary column and high-performance liquid chromatography (HPLC)/tandem mass spectrometry (MS/MS) detection for the determination of six butyrophenone derivatives (moperone, floropipamide, haloperidol, spiroperidol, bromperidol, and pimozide) in human plasma samples. The six butyrophenones were extracted by repeatedly aspirating and dispensing plasma sample solutions on a DB-17 capillary column (60 cm × 0.32 mm i.d., film thickness 0.25 μm). The analytes retained on the inner surface of the capillary column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. Extraction efficiencies ranged from 12.7% to 31.8% for moperone, spiroperidol, and pimozide, and from 1.08% to 4.86% for floropipamide, haloperidol, and bromperidol. The regression equations for all compounds showed excellent linearity, ranging from 0.05 to 50 ng/0.1 mL of plasma, except for moperone and spiroperidol (0.01 to 50 ng/0.1 mL). The limits of detection and quantification in plasma for each drug were 0.03–0.2 and 0.1–0.5 ng/mL, respectively. The intra- and inter-day coefficients of variation for all compounds in plasma were not greater than 13.7%.     

The reaction of 1,2-diiodo-tetrafluoroethane with sulfur trioxide

As an extension of our studies on the reaction of I(CF₂CF₂)_nI (n = 2 and 3) with sulfur trioxide¹⁾, the reaction of 1,2-diiodo-tetrafluoroethane with sulfur trioxide was studied.1,2-Diiodo-tetrafluoroethane was reacted with an excess of sulfur trioxide at reaction temperature ranging from 0°C to 115°C.The products were not the expected iododifluoroacetyl fluoride and/ or oxalyl fluoride, but thermally stable derivatives with polysulfate structures.These derivaties could be converted nearly quantitatively into iododifluoroacetyl fluoride and ethyl iododifluoroacetate by potassium fluoride and by ethanol, respectively.The possible structures of these derivatives will be discussed based on these results and ¹⁹F-NMR studies.     

Dense aqueous colloidal gold nanoparticles prepared from highly concentrated precursor solution

Gold nanoparticles were fabricated by reduction of highly concentrated Au(III) ions (200 mM) with casein proteins from milk. The gold nanoparticles were converted to nanoparticle-powders after washing and subsequent vacuum drying without aggregation. The nanoparticle-powders completely re-dispersed in aqueous solution, and stable colloidal gold nanoparticles were obtained. UV-vis extinction spectra and dynamic light scattering (DLS) measurements revealed that large assemblies (size, ca. 3 μm) and subaggregates (size, <0.5 μm) composed of gold nanoparticle-casein protein chain-Au(III) ion were dynamically formed and disintegrated over the course of the growth of the gold nanoparticles. Fourier transform infrared (FT-IR) spectra indicated conformational changes of casein proteins induced by the interaction of casein protein-Au(III) ion and -gold nanoparticle. Finally, rapid, one-pot, and highly concentrated synthetic procedures of gold and silver nanoparticle powders protected by casein (mean diameters below 10 nm) were successfully developed using 3-amino-1-propanol aqueous solutions as reaction media. Dense colloidal gold (40 g L(-1)) and silver (22 g L(-1)) nanoparticle aqueous solutions were obtained by re-dispersing the metal nanoparticle powders.     

Molecularly imprinted solid-phase extraction for the selective determination of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs in human whole blood by gas chromatography-mass spectrometry

A novel method is described for the extraction of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxy-methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine, and 3,4-(methylenedioxyphenyl)-2-butanamine, from human whole blood using molecularly imprinted solid-phase extraction as highly selective sample clean-up technique. Whole blood samples were diluted with 10 mmol/L ammonium acetate (pH 8.6) and applied to a SupelMIP-Amphetamine molecularly imprinted solid-phase extraction cartridge. The cartridge was then washed to eliminate interferences, and the amphetamines of interest were eluted with formic acid/methanol (1:100, v/v). After derivatization with trifluoroacetic anhydride, the analytes were quantified using gas chromatography-mass spectrometry. Recoveries of the seven amphetamines spiked into whole blood were 89.1-102%. The limits of quantification for each compound in 200 μL of whole blood were between 0.25 and 1.0 ng. The maximum intra- and inter-day coefficients of variation were 9.96 and 13.8%, respectively. The results show that methamphetamine, amphetamine, and methylenedioxyphenylalkyl-amine designer drugs can be efficiently extracted from crude biological samples such as whole blood by molecularly imprinted solid-phase extraction with good reproducibility. This extraction method will be useful for the pretreatment of human samples before gas chromatography-mass spectrometry.     

Determination of dextromethorphan in human plasma using pipette tip solid-phase extraction and gas chromatography-mass spectrometry

Dextromethorphan was extracted from human plasma samples (100 μL) using MonoTip C₁₈ tips, which are packed with C₁₈-bonded monolithic silica gel that is attached to the inside of the tip. The samples, which contained dextromethorphan and trimeprazine as an internal standard (IS), were mixed with 200 μL of distilled water and 50 μL of 1 mol/L glycine–sodium hydroxide buffer (pH 10). The mixture was extracted to the C₁₈ phase of the tip by 20 sequential aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C₁₈ phase were then eluted with methanol by five sequential aspirating/dispensing cycles. The eluate was injected directly into a gas chromatograph and detected by a mass spectrometer with selected ion monitoring in positive electron ionization mode. An Equity-5 fused silica capillary column (30 m × 0.32 mm i.d., film thickness 0.5 μm) gave adequate separation of the dextromethorphan, IS, and impurities. The recoveries of dextromethorphan and the IS spiked into plasma were >87.4%. The regression equation for dextromethorphan showed excellent linearity from 2.5 to 320 ng/mL of plasma, and the limit of detection was 1.25 ng/mL of plasma. The intraday and interday coefficients of variation were less than 10.5% and 14.7%, respectively. The accuracy ranged from 91.9% to 107%. The validated method was successfully used to quantify the plasma concentration of dextromethorphan in a human subject after oral administration of the drug.     

Submillimeter wave esr and far infrared spectroscopy measurements of CuGeO3

Submillimeter wave ESR and far infrared transmission measurements of first inorganic spin-Peierls system CuGeO₃ have been performed using the single crystals. Our new results are discussed in connection with the magnetic properties of the spin-Peierls systems and the recent neutron measurements of CuGeO₃.     

杉木优树大量繁殖技术的研究

以１８年生杉木优树嫁接苗（一年生）为外植体进行离体培养,茎段的最高分化率为６９％,侧芽的最高分化率为４０％。以茎段为外植体,在改良的ＭＳ（氮元素减半）＋ＢＡＰ２．０ｍｇ／Ｌ＋ＩＢＡ１．０ｍｇ／Ｌ的培养基上,平均每个茎段可诱导不定芽３～４个。在继代培养中,以改良的ＧＤ培养基加高浓度的ＢＡＰ６．７ｍｇ／Ｌ,平均每个茎段可诱导不定芽１１～１３个,然后在ＭＳ培养基上生长;在继代培养中激素浓度一般由低到高,再由高到低的循环,可以明显提高繁殖率。在生根培养中,以ＭＳ培养基（氮元素减半）加ＩＢＡ１．５ｍｇ／Ｌ,根的诱导率在４４％。     

A new BOD estimation method employing a double-mediator system by ferricyanide and menadione using the eukaryote Saccharomyces cerevisiae

A new biochemical oxygen demand (BOD) sensing method employing a double-mediator (DM) system coupled with ferricyanide and a lipophilic mediator, menadione and the eukaryote Saccharomyces cerevisiae has been developed. In this study, a stirred micro-batch-type microbial sensor with a 560 μL volume and a two-electrode system was used. The chronamperometric response of this sensor had a linear response between 1 μM and 10 mM hexacyanoferrate(II) (r² = 0.9995, 14 points, n = 3, average of relative standard deviation and R.S.D._av = 1.3%). Next, the optimum conditions for BOD estimation by the DM system (BOD_DM) were investigated and the findings revealed that the concentration of ethanol, used to dissolve menadione, influenced the sensor response and a relationship between the sensor output and glucose glutamic acid concentration was obtained over a range of 6.6-220 mg O₂ L⁻¹ (five points, n = 3, R.S.D._av 6.6%) when using a reaction mixture incubated for 15 min. Subsequently, the characterization of this sensor was studied. The sensor responses to 14 pure organic substances were compared with the conventional BOD₅ method and other biosensor methods. Similar results with the BOD biosensor system using Trichosporon cutaneum were obtained. In addition, the influence of chloride ion, artificial seawater and heavy metal ions on the sensor response was investigated. A slight influence of 20.0 g L⁻¹ chloride ion and artificial seawater (18.4 g L⁻¹ Cl⁻) was observed. Thus, the possibility of BOD determination for seawater was suggested in this study. In addition, no influence of the heavy metal ions (1.0 mg L⁻¹ Fe³⁺, Cu²⁺, Mn²⁺, Cr³⁺ and Zn²⁺) was observed. Real sample measurements using both river water and seawater were performed and compared with those obtained from the BOD₅ method. Finally, stable responses were obtained for 14 days when the yeast suspension was stored at 4 °C (response reduction, 93%; R.S.D. for 6 testing days, 9.1%).