气相-质谱联用分析冠心苏合丸中的挥发性组分

 采用气相 质谱联用对冠心苏合丸及药材中的挥发性成分进行了分析。采用选择离子监测法 ,以水杨酸甲酯为内标 ,对冠心苏合丸中的两个指标成分冰片和苯甲酸苄酯进行了定量测定。冰片和苯甲酸苄酯的平均加标回收率分别为 91 7%和 89 7% ,RSD分别为 5 6 %和 2 3%。     

Tandem Transesterification–Esterification Reactions Using a Hydrophilic Sulfonated Silica Catalyst for the Synthesis of Wintergreen Oil from Acetylsalicylic Acid Promoted by Microwave Irradiation

SiO₂–SO₃H, with a surface area of 115 m²/g and pore volume of 0.38 cm³g⁻¹, and 1.32 mmol H⁺/g was used as a 20% w/w catalyst for the preparation of methyl salicylate (wintergreen oil or MS) from acetylsalicylic acid (ASA). A 94% conversion was achieved in a microwave reactor over 40 min at 120 °C in MeOH. The resulting crude product was purified by flash chromatography. The catalyst could be reused three times.     

Studies on the synthesis of heterocyclic compounds. Part VI. The action of methyl salicylate on some 5-aminopyrazoles

Some 1-phenyl-3-R-5-aminopyrazoles reacted with methyl salicylate to give N-(1-phenyl-3-R-pyrazol-5-yl)-2-methoxybenzamides ( 3a,b,c ), 1-phenyl-2-methyl-3-R-salicyloilimino-3-pyrazolines ( 4a,b,c ) together with 1-phenyl-3-R-5-methylamino pyrazoles ( 5a,b,c ). The structures of the new compounds 3 and 4 were determined on the basis of analytical and spectroscopic data as well as on the acid hydrolysis products.     

Ion/molecule reactions in a miniature RIT mass spectrometer

Ion/molecule reactions were explored in a newly developed miniature mass spectrometer fitted with a rectilinear ion trap (RIT) mass analyzer. The tandem mass spectrometry performance of this instrument is demonstrated using collision induced dissociation (CID) and ion/molecule reactions. The latter includes Eberlin transacetalization reactions and electrophilic additions. Selective detection of the chemical warfare simulant dimethyl methyl phosphonate (DMMP) was achieved through selective Eberlin reactions of its characteristic phosphonium fragment ion CH3OP(+)(O)CH3 (m/z 93), with 1,4-dioxane or 1,3-dioxolane. Efficient adduct formation as a result of electrophilic attack by the phosphonium ion on various nucleophilic reagents, including 1,1,3,3-tetramethyl urea, methanesulfonic acid methyl ester, dimethyl sulfoxide and methyl salicylate, was also observed using the RIT device. The product ions of these reactions were analyzed using CID and the characteristic fragmentation patterns of the ionic addition products were recorded using multiple-stage experiments in the miniature RIT instrument. This study clearly demonstrates that a small, home-built, miniature RIT mass spectrometer can be used to perform analytically useful ion/molecule reactions and also that instruments like this have the potential to provide a portable platform for in situ detection of organophosphorus esters and related compounds with high specificity using tandem mass spectrometry.     

Improved detection of low vapor pressure compounds in air by serial combination of single-sided membrane introduction with fiber introduction mass spectrometry (SS-MIMS-FIMS)

The use of two methods in tandem, single-sided membrane introduction mass spectrometry (SS-MIMS) and fiber introduction mass spectrometry (FIMS), is presented as a technique for field analysis. The combined SS-MIMS-FIMS technique was employed in both a modified commercial mass spectrometer and a miniature mass spectrometer for the selective preconcentration of the explosive simulant o-nitrotoluene (ONT) and the chemical warfare agent simulant, methyl salicylate (MeS), in air. A home-built FIMS inlet was fabricated to allow introduction of the solid-phase microextraction (SPME) fiber into the mass spectrometer chamber and subsequent desorption of the trapped compounds using resistive heating. The SS-MIMS preconcentration system was also home-built from commercial vacuum parts. Optimization experiments were done separately for each preconcentration system to achieve the best extraction conditions prior to use of the two techniques in combination. Improved limits of detection, in the low ppb range, were observed for the combination compared to FIMS alone, using several SS-MIMS preconcentration cycles. The SS-MIMS-FIMS response for both instruments was found to be linear over the range 50 to 800 ppb. Other parameters studied were absorption time profiles, effects of sample flow rate, desorption temperature, fiber background, memory effects, and membrane fatigue. This simple, sensitive, accurate, robust, selective, and rapid sample preconcentration and introduction technique shows promise for field analysis of low vapor pressure compounds, where analyte concentrations will be extremely low and the compounds are difficult to extract from a matrix like air.     

Identification of methyl salicylate as the principal volatile component in the methanol extract of root bark of Securidaca longepedunculata Fers

Securidaca longepedunculata Fers (Polygalaceae) is commonly used as a medicine in many parts of Africa and shows promise for protecting stored grain against insect pests. Analysis of a methanol extract of the root bark by gas chromatography linked to mass spectrometry (GC/MS) showed a major component accounting for over 90% of the volatile material. This was identified as methyl 2-hydroxybenzoate (methyl salicylate) by comparison of the GC retention times and mass spectrum with those of synthetic standards. This conflicts with an earlier report that the major component is methyl 4-hydroxybenzoate. Two minor components had mass spectra characteristic of 2-hydroxybenzoate esters and were identified as methyl 2-hydroxy-6-methoxybenzoate and its benzyl analogue, again conflicting with an earlier report.     

Potential psychotropic agents. 7-Chloro-9-phenyl-3,3-diethyl-3H-pyrazolo-[5, 1-b]quinazolin-10-ium-2-olate and 9-Chloro-2,3,4,5-tetrahydro-1-methyl-3,3-diethyl-7-phenyl-1H-benzo-1,5,6-triazonine-2,4-dione

2-Amino-5-chloro-α-phenylbenzylidene hydrazone ( 1 ) or its methyl derivative 2 or acetyl derivative 10 react with diethylmalonic esters to give the corresponding malonyl derivatives 3, 4 and 8 . These esters were hydrolyzed to the acids 5 and 6 . Treating 5 with dehydrating agents the mesoionic compound 7-chloro-9-phenyl-3,3-diethyl-3H-pyrazolo[5,1-b]quinazolin-10-ium-2-olate (14) was obtained, while the methyl derivative 6 afforded the desired 9-chloro-2,3,4,5-tetrahydro-1-methyl-3,3-diethyl-7-phenyl-1H-benzo-1,5,6-triazonine-2,4-dione ( 17 ). Some derivatives of these compounds were also described. The structures of the new compounds were confirmed by an alternative synthesis and by mass and prnr spectral data.     

Characterization of a novel trace-level impurity in lisinopril using multi-stage mass spectrometry

An impurity in the bulk drug lisinopril was detected by simple reversed-phase high-performance liquid chromatography (HPLC). This trace-level impurity was rapidly identified as 2-(2-oxo-azocan-3-ylamino)-4-phenyl- butyric acid on the basis of the on-line multi-stage mass spectrometric evidence, and the proposed structure was further confirmed by multi-stage mass spectrometry of lisinopril and three related compounds.     

自身化学电离质谱法测定(赤/苏)-2-甲基苯丙二醇胺类衍生物的准确质量

采用自身化学电离离子化／付里叶变换质谱法（ＳＣＩ／ＦＴＭＳ）测定了（赤／苏）－２－甲基苯丙二醇胺类衍生物共２４个样品的质子化分子离子的准确质量,与理论值相比,相对误差均小于５×１０－６级,结果表明ＳＣＩ／ＦＴＭＳ是测定电离过程中不稳定化合物元素组成的简便、快速、准确的方法。     

自身化学电离质谱法测定(赤/苏)-2-甲基苯丙二醇胺类衍生物的准确质量

采用自身化学电离离子化/付里叶变换质谱法(SCI/FTMS)测定了(赤/苏)-2-甲基苯丙二醇胺类衍生物共24个样品的质子化分子离子的准确质量,与理论值相比,相对误差均小于5×10^-6级,结果表明SCI/FTMS是测定电离过程中不稳定化合物元素组成的简便、快速、准确的方法。     

Analysis of gaseous toxic industrial compounds and chemical warfare agent simulants by atmospheric pressure ionization mass spectrometry

The suitability of atmospheric pressure chemical ionization mass spectrometry as sensing instrumentation for the real-time monitoring of low levels of toxic compounds is assessed, especially with respect to public safety applications. Gaseous samples of nine toxic industrial compounds, NH3, H2S, Cl2, CS2, SO2, C2H4O, HBr, C6H6 and AsH3, and two chemical warfare agent simulants, dimethyl methylphosphonate (DMMP) and methyl salicylate (MeS), were studied. API-MS proves highly suited to this application, with speedy analysis times (<30 seconds), high sensitivity, high selectivity towards analytes, good precision, dynamic range and accuracy. Tandem MS methods were implemented in selected cases for improved selectivity, sensitivity, and limits of detection. Limits of detection in the parts-per-billion and parts-per-trillion range were achieved for this set of analytes. In all cases detection limits were well below the compounds' permissible exposure limits (PELs), even in the presence of added complex mixtures of alkanes. Linear responses, up to several orders of magnitude, were obtained over the concentration ranges studied (sub-ppb to ppm), with relative standard deviations less than 3%, regardless of the presence of alkane interferents. Receiver operating characteristic (ROC) curves are presented to show the performance trade-off between sensitivity, probability of correct detection, and false positive rate. A dynamic sample preparation system for the production of gas phase analyte concentrations ranging from 100 pptr to 100 ppm and capable of admixing gaseous matrix compounds and control of relative humidity and temperature is also described.     

Bis (trans-cinnamaldehyde) ethylene diimine dibromonickel (II) complex as a neutral carrier for salicylate-selective liquid membrane and coated graphite sensors

A salicylate PVC-based membrane (SPME) and a coated graphite membrane (SCGE) electrodes by using a new tetracoordinate organonickel complex as ion carrier were prepared. Both sensors show a Nernstian response to salicylate ions over a very wide concentration ranges (1.0×10⁻⁵-1.0×10⁻¹ M for SPME and 1.0×10⁻⁶-1.0×10⁻² M for SCGE) in the pH of 7.0. The best selectivities were obtained for the membrane incorporating 30% PVC, 63% plasticizer, 2% cationic additive and 5% ionophore. The electrodes possess satisfactory reproducibility, very short response time (∼10 s) in the whole concentration ranges, and excellent discriminating ability for salicylate ions with respect to the most common organic and inorganic anions. The detection limits of proposed sensors are 5.0×10⁻⁶ and 7.0×10⁻⁷ M for SPME and SCGE, respectively. The electrodes were successfully used for determination of salicylate in biological samples.     

Synthesis of some novel 3,4,5-trisubstituted triazole derivatives bearing quinoline ring and evaluation of their antimicrobial activity

Abstract

Some new 3,4,5-trisubstituted 1,2,4-triazole derivatives were synthesized and studied for their antimicrobial activity. The lead compounds were obtained starting from 8-hydroxyquinoline and ethyl 2-chloroacetate. The obtained ester compound (1) first reacted with hydrazine hydrate (2) then with phenyl isothiocyanate (3). Ring closure by KOH led to 3-mercapto-1,2,4-triazole derivative (4). Lastly, it reacted with 2-chloro-N-(substituted (benzo)/thiazole)acetamide derivatives to obtain the final compounds (5a–j). The structural elucidation of the compounds was performed by ¹H NMR and ¹³C NMR spectroscopy and high resolution mass spectrometry techniques and elemental analysis. The synthesized compounds were investigated for their antimicrobial activities against seven bacteria and four fungi. As a result of the activity studies, it was observed that compounds N-(6-nitrobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5a) and N-(6-fluorobenzothiazol-2-yl)-2-[[4-phenyl-5-((quinolin-8-yloxy)methyl)-4H-1,2,4-triazol-3-yl]thio]acetamide (5d) were the most active molecules. Also, the antifungal activity of the compounds was found to be higher than their antibacterial activity although lower than the standard drug’s potential. Additionally, the physicochemical properties of the compounds were calculated which were evaluated to be at a suitable range for oral administration.     

Application of Tetra Cyclohexyl Tin(IV) as an Anionic Carrier for the Construction of a New Salicylate Membrane Sensor

A new tin complex namely tetracyclohexyl tin(IV) (TCHT) was synthesized and used as the ion carrier for the construction of a highly selective salicylate sensor. This sensor shows a Nernstian response to salicylate ions over a very wide concentration (1.0 × 10^?7–1.0 × 10^?1 M) in a pH range of 5.5–10.5. The optimum selectivity and response could be obtained for a membrane incorporating 30% PVC, 61% BA, 3% of cationic additive (HTAB) and 6% of TCHT. The response time of the electrode is very short in the whole concentration range (15 s). The electrode also shows an excellent discriminating ability for salicylate ions with respect to the most common organic and inorganic anions including chloride, sulfate, nitrate, nitrite, cyanide, sulfite, iodide, thiocyanate, phosphate, acetate, oxalate, citrate, and tartarate ions. The detection limit of the proposed sensor is 8.0 × 10^?8 M. The electrode was successfully used for determining the concentration of salicylate ion in synthetic serums.     

Structures and fluorescence of secondary products produced from the cope-knoevenagel reaction of 2-phenylpropionaldehyde with methyl cyanoacetate

The Cope-Knoevenagel reaction of 2-phenylpropionaldehyde ( 7 ) with methyl cyanoacetate ( 8 ) produced methyl (E)-2-cyano-4-phenylpent-2-enoate ( 9 ) and the two highly fluorescent secondary products, 2-amino-3-carbomethoxy-6-phenyl-4-(1-phenylethyl)pyridine ( 10 ) and 3-cyano-6-phenyl-4-(1-phenylethyl)-2-pyridone ( 11 ). The structure of 10 was determined by X-ray crystallography while the structure of 11 was confirmed by the conversion of 9 into 11 . The mechanism of their formation is discussed. Fluorescence of 10 and 11 and the related compounds are also described.     

Absolute photoionization cross-section of the methyl radical

The absolute photoionization cross-section of the methyl radical has been measured using two completely independent methods. The CH3 photoionization cross-section was determined relative to that of acetone and methyl vinyl ketone at photon energies of 10.2 and 11.0 eV by using a pulsed laser-photolysis/time-resolved synchrotron photoionization mass spectrometry method. The time-resolved depletion of the acetone or methyl vinyl ketone precursor and the production of methyl radicals following 193 nm photolysis are monitored simultaneously by using time-resolved synchrotron photoionization mass spectrometry. Comparison of the initial methyl signal with the decrease in precursor signal, in combination with previously measured absolute photoionization cross-sections of the precursors, yields the absolute photoionization cross-section of the methyl radical; sigma(CH3)(10.2 eV) = (5.7 +/- 0.9) x 10(-18) cm(2) and sigma(CH3)(11.0 eV) = (6.0 +/- 2.0) x 10(-18) cm(2). The photoionization cross-section for vinyl radical determined by photolysis of methyl vinyl ketone is in good agreement with previous measurements. The methyl radical photoionization cross-section was also independently measured relative to that of the iodine atom by comparison of ionization signals from CH3 and I fragments following 266 nm photolysis of methyl iodide in a molecular-beam ion-imaging apparatus. These measurements gave a cross-section of (5.4 +/- 2.0) x 10(-18) cm(2) at 10.460 eV, (5.5 +/- 2.0) x 10(-18) cm(2) at 10.466 eV, and (4.9 +/- 2.0) x 10(-18) cm(2) at 10.471 eV. The measurements allow relative photoionization efficiency spectra of methyl radical to be placed on an absolute scale and will facilitate quantitative measurements of methyl concentrations by photoionization mass spectrometry.     

Capillary electrophoresis/mass spectrometry: a promising tool for the control of some physiologically hazardous compounds. I-derivatives of 3-quinuclidinol

A method based on the coupling of capillary electrophoresis with mass spectrometry (CE/MS) was developed for the monitoring of 3-quinuclidinol and its four N-alkyl derivatives (methyl, ethyl, propyl and isopropyl derivatives). A fragmentation study (collision-induced dissociation of ions in an ion trap) and optimization of the ion optics set-up for CE/MS experiments using direct infusion of a methanolic solution of the standards into the mass spectrometer were carried out in advance. Molecular ions of all quaternary compounds and the quasi-molecular ion [M + H]+ of free 3-quinuclidinol prevail in the mass spectra. In the MS/MS of propyl and isopropyl derivatives, the elimination of the alkyl chain dominates, leading to the ion at m/z 128. The fragmentation of the other compounds is more complex. Previous CE separation of the mixture of isobaric propyl and isopropyl derivatives is necessary for their unambiguous identification. A 10 mM ammonium acetate buffer (pH 4.0) is the optimum running electrolyte, allowing the CE separation of methyl, ethyl, propyl and isopropyl derivatives. A 0.5% (v/v) solution of acetic acid in methanol provides sufficient detection sensitivity when used as the sheath liquid. Limits of detection of 0.1 ppm for 3-quinuclidinol and 0.05 ppm for quaternary derivatives were achieved under the optimum conditions. The optimized method was applied to the determination of 3-quinuclidinol and related quaternary derivatives spiked into a sample of pond water. The experimental set-up for CE/MS/MS was investigated, which strongly increases the identification capability of the technique.     

Simple gas chromatographic method for the stereodifferentiation of methyl nilate, a chiral alpha-methyl-beta-hydroxy ester

The four stereoisomers of methyl nilate, methyl 3-hydroxy-2-methylbutanoate, have been separated and analyzed by the direct simultaneous achiral-chiral high-resolution gas chromatography (HRGC) and also by the chiral high-resolution gas chromatography-time-of-flight mass spectrometry (HRGC-TOF-MS). The method involved the use of DB-5 and CP Chirasil-Dex CB columns. The elution sequences on the two columns were determined and are reported. The one-step GC method allows the identification by retention data and simultaneously to determine unequivocally the absolute configuration of nilic acid moieties contained in minor complex natural products without previous isolation, as part of a general strategy for the structure determination of the compounds.     

Analysis of residual solvents in pharmaceuticals with purge-and-membrane mass spectrometry

A method using purge-and-membrane mass spectrometry (PAM-MS) was developed for the analysis of residual solvents in pharmaceutical products. The method combines dynamic headspace and membrane inlet mass spectrometry. The limits of detection for the compounds studied, benzene, toluene, chloroform, 2-pentene and 2-methyl- and 3-methylpentane, were 0.05-0.1 mg/kg. In quantitative analysis the method showed good linearity (r(2) > 0.998) and acceptable within-day (RSD = 7.9-18%) and between-day (RSD = 6.8-10%) repeatability. The PAM-MS method combined with the custom-made Solver program was compared with a method using purge-and-trap gas chromatography/mass spectrometry (P&T-GC/MS) for identification of residual solvents from authentic samples. The results showed that PAM-MS/Solver provides reliable identification of the main volatile organic compounds (VOCs) in the pharmaceuticals, but VOCs with low concentrations (below 0.5 mg/kg) were better identified by P&T-GC/MS. Other advantages of the PAM-MS method were short analysis times and non-requirement for pre-treatment of samples.     

Structural analysis and biomedical potential of novel salicyloyloxy estrane derivatives synthesized by microwave irradiation

New estrane salicyloyloxy or D-homo derivatives were synthesized under microwave (MW) or conventional heating from estrane precursors and methyl salicylate. The MW technique provides advantages regarding product yield and reaction time, and represents a more environmentally friendly approach than conventional heating. Considering the biomedical potential of estrane compounds, we evaluated the antioxidant activity and cytotoxicity of synthesized estrane derivatives in a series of in vitro tests, as well as their 3β-hydroxysteroid dehydrogenase/Δ⁵ → Δ⁴ isomerase (3βHSD) and 17β-hydroxysteroid dehydrogenase types 1, 2 and 3 (17βHSD1, 17βHSD2 and 17βHSD3) inhibition potentials. In DPPH tests, 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate displayed antioxidant potential, while all compounds exhibited OH radical neutralization activity. 3-Oxoestr-4-en-17β-yl salicylate showed strong cytotoxicity against MDA-MB-231 breast cancer cells, while 17-oxoestra-1,3,5(10)-trien-3-yl salicylate, estra-1,3,5(10)-triene-3,17β-diyl 3-benzoate 17-salicylate and 3-benzyloxy-17-salicyloyloxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile showed the strongest inhibition of PC-3 prostate cancer cell growth. 3-Hydroxyestra-1,3,5(10)-trien-17β-yl salicylate was the best inhibitor of 17βHSD2, suggesting potential use in treating pathological conditions associated with estrogen depletion. For 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate and 3-oxoestr-4-en-17β-yl salicylate, X-ray crystal structure analysis and molecular energy optimization were performed to define their conformations and energy minima. Very good overlap in the region of the steroidal nucleus was observed for the molecular structures of each analyzed molecule in the crystalline state and after energy optimization, while conformer analysis indicates conformational flexibility in the form of rotation around the C17···O2 bond. Structural geometry analysis for these compounds shows that the region of ring A in steroids, and especially the C3 atom functional group, is important structural features concerning antiproliferative activity against MDA-MB-231 cells.