含氮杂环及其衍生物的氮氧化方法研究进展

含氮杂环及其衍生物中的N－氧化反应是合成许多精细化工产品，如日用化学 品、医药、农药的重要反应，但该反应选择性较高，只要求在杂环氮上进行氧化而 不影响分子其它部位，从氮杂环及其衍生物应用不同氧化剂选择性氧化综述了该类 化合物的N－氧化反应。     

Assessment of limits of detection and quantitation using calculation of uncertainty in a new method for water determination

 An approach to the assessment of the limit of detection and the limit of quantitation using uncertainty calculation is discussed. The approach is based on the known evaluation of the limits of detection and quantitation as concentrations of the analyte equal to three and ten standard deviations of the blank response, respectively. It is shown that these values can be calculated as the analyte concentrations, for which relative expanded uncertainty achieves 66% and 20% of possible results of the analyte determination, correspondingly. For example, the calculation is performed for the validation of a new method for water determination in the presence of ene-diols or thiols, developed for analysis of chemical products, drugs or other materials which are unsuitable for direct Karl Fischer titration. A good conformity between calculated values and experimental validation data is observed. Received: 27 July 1998 · Accepted: 29 November 1998     

Degradation studies of quetiapine fumarate by liquid chromatography–diode array detection and tandem mass spectrometry methods

Quetiapine fumarate (QUE) is an antipsychotic agent with a chemical structure that is susceptible to degradation; therefore, it is important to study its stability using appropriate analytical tools. Knowledge of the stability profile of a drug is important because chemical degradation of its active component often results in a loss of potency, affecting its efficacy and safety. This current work reports degradation studies of QUE as drug substance, under different stress conditions such as oxidation, hydrolysis, heat, humidity and photolysis, by a stability‐indicating LC method. The chemical stability was evaluated using a simple HPLC/diode array detection method, with a core‐shell C₁₈ column under isocratic conditions, which allows the separation of all primary degradation products (DPs) in a short run time. QUE was mainly degraded under oxidative and hydrolytic conditions, with the formation of three and two DPs, respectively, which were identified by electrospray ionization–tandem mass spectrometry. The method was properly validated in terms of linearity, accuracy, precision, selectivity, robustness and quantitation limit. Commercial tablets containing 25 mg of QUE were quantified, with results obtained within the United States Pharmacopeia limits. The proposed method is suitable to assess the stability and perform routine analysis of QUE in pharmaceutical samples.     

Apparatus and method for interfacing capillary electrophoresis and chemiluminescence nitrogen detection for the analysis of nitrogen-containing compounds

We have developed an interface that allows the specific detection of nitrogen-containing compounds by using a chemiluminescence nitrogen detector. The feasibility of using this interface was demonstrated by separating and detecting two nitrogen-containing compounds, p-aminosalicylic acid and L-phenylalanine. Although baseline separation was achieved, the theoretical plates were lower when compared to UV detection (25000 vs. approximately 85000). A sensitivity of 75 ng (approximately 500 pmol) per injection was achieved with this system which is adequate for pharmaceutical and biotech applications.     

Chemiluminescence nitrogen detection in ion chromatography for the determination of nitrogen-containing anions

Chemiluminescence nitrogen detection (CLND) provides equimolar response for nitrogen-containing ions such as nitrate, nitrite, cyanide, ammonium and tetradecyltrimethylammonium. Only azide yields a lower response. Nitrite, azide and nitrate are separated on a Dionex AS11 column using 5 mM NaOH as eluent with a 3 μM (1 ng N) limit of detection. Matrices, such as 1:10 diluted seawater, do not degrade these detection limits. CLND also provides equally sensitive (limit of detection 3 μM, 78 ppb) detection of weak acids such, as cyanide, which yield poor sensitivity with suppressed conductivity detection.     

Thermal and photochemical oxidation of self-assembled monolayers on alumina particles exposed to nitrogen dioxide

Alumina is an important component of airborne dust particles as well as of building materials and soils found in the tropospheric boundary layer. While the uptake and reactions of oxides of nitrogen and their photochemistry on alumina have been reported in the past, little is known about the chemistry when organics are also present. Fourier transform infrared (FTIR) spectroscopy at ～23 °C was used to study reactions of NO(2) on γ-Al(2)O(3) particles that had been derivatized using 7-octenyltrichlorosilane to form a self-assembled monolayer (SAM). For comparison, the reactions with untreated γ-Al(2)O(3) were also studied. In both cases, the particles were exposed to water vapor prior to NO(2) to provide adsorbed water for reaction. As expected, surface-bound HONO, NO(2)(-), and NO(3)(-) were formed. Surprisingly, oxidation of the organic by surface-bound nitrogen oxides was observed in the dark, forming organo-nitrogen products identified as nitronates (R(2)C[double bond, length as m-dash]NO(2)(-)). Oxidation was more rapid under irradiation (λ > 290 nm) and formed organic nitrates and carbonyl compounds and/or peroxy nitrates in addition to the products observed in the dark. Mass spectrometry of the gas phase during irradiation revealed the production of NO, CO(2), and CO. These studies provide evidence for oxidation of organic compounds on particles and boundary layer surfaces that are exposed to air containing oxides of nitrogen, as well as new pathways for the formation of nitrogen-containing compounds on these surfaces.     

Determination of arsenic in seafood by focused microwave digestion and hydride generation-atomic fluorescence detection

A new method was developed for total arsenic determination in seafood products such as oysters, mussels, tuna fish, and algae. Matrix decomposition and oxidation to arsenate of all the arsenic compounds in the product were completed in 25 min by using a 3-step program of focused microwaves (40-120 W) with nitric and sulfuric acids. Quantitation was performed by hydride generation-atomic fluorescence detection (HG-AFS). Results of method optimization are presented and discussed. A detection limit <125 microg/kg arsenic was obtained; the quantitation limit was close to 400 microg/kg, with repeatability and reproducibility <5% relative standard deviation. Validation was performed by analyzing 4Reference Materials (arsenic concentration expressed as mg/kg): The National Institute of Standards and Technology SRM 1566a Oyster tissue (14.0 +/- 1.2); the Bureau Community of Reference (now Standard Measurements & Testing Program) CRM 278 Mussel tissue (5.9 +/- 0.2) and CRM 627 Tuna fish (4.8 +/- 0.3); and the International Atomic Energy Agency RM 140 Fucus sample (44.3 +/- 2.1).     

Analysis of volatile organic compounds in fuel oil by headspace GC-MS

Fuel oils are mostly used in marine applications and in power plants. They are known to contain hazardous volatile organic compounds (VOCs) that are of health and environmental importance. Chlorinated compounds, phenolic compounds, styrenes, indene, dicyclopentadiene, dihydrodicyclopentadiene, cumene, benzene, toluene, ethylbenzene and xylenes are some of the VOCs that have found their way into fuel oil through various streams during bunkering operation. Chromatographic analysis of VOCs in the presence of complex matrices in fuel oil is one of the major challenges encountered when dealing with products of that nature. An analytical procedure using automated static headspace gas chromatography–mass spectrometry was developed for the analysis of these compounds in fuel oil. Styrene D8 and phenol D6 were used as internal standards for quantitation. Phenol D6 was used for the quantitation of phenolic compounds, while styrene D8 was used for the quantitation of other target analytes. The influence of headspace parameters on analyte response such as temperature, incubation time and sample amount were all investigated and optimised. Linear calibration curves were achieved for all components with determination coefficients R² > 0.995. Repeatability, limit of detection, limit of quantitation and recovery were reported. The matrix effect in fuel oil was minimised by 1:1 dilution with mineral oil. This method was successfully applied to the analysis of commercial samples.     

A novel method for the calibration of Kováts retention indices using n-alkanes with a thermionic nitrogen-phosphorus specific detector

This paper describes a novel method for the detection of compounds that do not contain nitrogen or phosphorus by a thermionic nitrogen-phosphorus specific detector (NPD), which normally detects only nitrogen- or phosphorus-containing compounds. This method allows for the calibration of gas chromatographic columns with NPD detectors using n-alkanes instead of nitrogen-containing drug mixtures. This results in a more rapid and accurate calibration for the calculation of relative retention indices (RRI), such as Kováts indices, than was previously possible when employing an NPD detector. The proposed method describes the temporary conversion of the NPD detector into a detector with properties much like a flame ionization detector. After a deliberate increase in the hydrogen gas flow rate to the thermionic bead from 4 ml/min to 8 ml/min, the n-alkanes (containing no nitrogen) can be detected and used as RRI calibrators. Once the column has been calibrated, the hydrogen gas flow rate is lowered to the normal rate of 4 ml/min. The detector then behaves as a normal NPD, no longer detecting the n-alkanes.     

Total nitrogen in wastewater analysis: Comparison of Devarda’s alloy method and high temperature oxidation followed by chemiluminescence detection

Two methods for determining total nitrogen (TN) contents of complex wastewaters were compared: Devarda’s alloy method and a method involving high temperature oxidation (HTO) followed by chemiluminescence detection (CLD). In the latter multiple standard additions were used for quantification purposes since the CLD response was found to be dependent on the structure of the analysed nitrogen-containing compounds. For both methods, sample dilution steps were necessary to achieve acceptable accuracy. The accuracies for selected compounds used in tests were within the 65–105% range. In a long-term interlaboratory investigation the HTO-CLD method yielded significantly (p < 0.05) higher results than Devarda’s alloy method and greater precision (within-assay repeatability approximately 1% RSD, while the corresponding within-day repeatability for Devarda’s alloy method was approximately 7% RSD).     

Method for the simultaneous determination of monoaromatic and polycyclic aromatic hydrocarbons in industrial effluents using dispersive liquid–liquid microextraction with gas chromatography–mass spectrometry

We present a new method for simultaneous determination of 22 monoaromatic and polycyclic aromatic hydrocarbons in postoxidative effluents from the production of petroleum bitumen using dispersive liquid–liquid microextraction coupled to gas chromatography and mass spectrometry. The eight extraction parameters including the type and volume of extraction and disperser solvent, pH, salting out effect, extraction, and centrifugation time were optimized. The low detection limit ranging from 0.36 to 28 μg/L, limit of quantitation (1.1–84 μg/L), good reproducibility, and wide linear ranges, as well as the recoveries ranging from 71.74 to 114.67% revealed that the new method allows the determination of aromatic hydrocarbons at low concentration levels in industrial effluents having a very complex composition. The developed method was applied to the determination of content of mono‐ and polycyclic aromatic hydrocarbons in samples of raw postoxidative effluents in which 15 compounds were identified at concentrations ranging from 1.21 to 1017.0 μg/L as well as in effluents after chemical treatment.     

A new HPLC-UV validated method for therapeutic drug monitoring of tyrosine kinase inhibitors in leukemic patients

Development and validation of simple, rapid, and reliable high-performance liquid chromatography (HPLC)-UV method for quantification of major tyrosine kinase inhibitors, imatinib, dasatinib, and nilotinib, in human plasma is presented. Chromatographic separation of the drugs is achieved on an RP-C(18) column at flow rate of 0.9 mL/min at 35°C; eluate is monitored at 267 nm. Mean intra-day and inter-day precision for all compounds are 2.5 and 13.3%; mean accuracy is 13.9%; extraction recovery ranges within 40.24 and 81.81%. Calibration curves range from 10 to 0.005 μg/mL. Limits of detection are 10 ng/mL for imatinib and nilotinib, 50 ng/mL for dasatinib; limits of quantitation are 50 ng/mL for imatinib and nilotinib, 100 ng/mL for dasatinib. Although this method allows the detection of dasatinib, levels found in patients plasma are close to the limit of detection, then below the limit of quantitation. Quantification with HPLC-mass spectrometry, then, is required for dasatinib to give a correct evaluation. In conclusion, the sensitivity of this new method is sufficient to perform therapeutic monitoring and pharmacokinetic studies of imatinib and nilotinib but not dasatinib in CML patients.     

Redox-potentiometric determination of peroxide value in edible oils without titration

Standard methods for peroxide value determination in edible oils, which are based on KI oxidation by the hydroperoxides and volumetric titration of the liberated iodine, have been improved using redox-potentiometric iodine determination without titration. Stages of the KI oxidation and redox-potentiometric measurements were combined in the same electrochemical cell. The limit of quantitation of the new method is 0.16 meq kg(-1), which allows the analysis of fresh refined oils. The method is simple, not time and labor consuming, and suitable for automation.     

Quantitative determination of antalarmin, a novel corticotropin-releasing hormone receptor-1 antagonist, in canine plasma by HPLC-MS

A simple and rapid method was developed for the quantitation of antalarmin from plasma using high performance liquid chromatography coupled with electrospray ionization mass spectrometry (ESI/MS). Separation of antalarmin from interfering compounds was achieved using reversed phase chromatography on a C-8 micro-column with an isocratic mobile phase comprised of 80% acetonitrile, 20% water, and 5 mM triethylamine. Detection by ESI/MS was accomplished in positive ion mode using single ion monitoring of the protonated molecular ions of antalarmin and its 13C2-isotopimer. The area ratio of the integrated peaks of interest in the extracted ion chromatogram was used for quantitation. The lower limit of detection was 1 picogram (pg) and the quantitation showed a linear response up to 4 nanograms loaded on column. To achieve acceptable accuracy at or around the limit of quantitation of 20 pg, a 1/x weighting was applied to the calibration data. Accuracy and precision variation for intra and inter-day validation were below the acceptable limit (15%) for pharmacokinetic studies.     

Stability-indicating high-performance liquid chromatographic assay of atorvastatin with fluorescence detection

The purpose of this work was to develop a sensitive, selective, and validated stability-indicating high-performance liquid chromatographic (LC) assay of atorvastatin (ATV) in bulk drug and tablet form. ATV was subjected to different stress conditions, including UV light, oxidation, acid-base hydrolysis, and temperature. ATV and its degradation products were analyzed on an Agilent Zorbax XDB C18 column using isocratic elution with acetonitrile-0.02 M sodium acetate, pH 4.2 (45 + 55, v/v) for 25 min. The samples were monitored with fluorescence (FL) detection at 282 nm (excitation)/400 nm (emission). The response ratio of FL to UV detection (at 247 nm) for ATV was 1.66. The method showed good resolution of ATV from its decomposition products. The photodegradation products were separated by silica gel thin-layer chromatography using double development with ethyl acetate-n-hexane-glacial acetic acid-methanol (40 + 55 + 0.5 + 4.5, v/v/v/v) followed by (39 + 55 + 0.5 + 5.5, v/v/v/v), and confirmed by LC-FL analysis. The FL response was linear over the investigated range for ATV. The linear range was 10-1200 ng/injection, and the limit of quantitation was 2.0 ng/injection.     

薄层色谱-火焰离子检测技术在重质油族组成分析中的应用

报道了ＴＬＣ－ＦＩＤ技术在重质油族组成分析中的应用。在本文提供的方法下,可对重质油中族组成（饱和烃,芳香烃写,胶质等）进行有效分离和检测。方法的重复性优于经典柱色谱。该技术居有快速,准确,样品及溶剂用量少等特点。在给定试验条件下,原油的种类和实际点样量不影响ＦＩＤ的响应值。     

Determination of hexamethylphosphoramide and other highly polar phosphoramides in water samples using reversed-phase liquid chromatography/electrospray ionization time-of-flight mass spectrometry

The widely used solvent hexamethylphosphoramide (HMPA) and its biological (metabolic) and chemical (abiotic) phosphoramide-based oxidation products may cause adverse health effects through occupational exposure and intake of contaminated groundwater. However, no current methods exist for the separation and the detection of the many polar HMPA oxidation products. Thus, we developed a new RPLC/ESI-TOF-MS method and further investigated the chromatographic performances of two columns (i.e., XTerra Phenyl and XBridge Phenyl). In addition, the impact of (forced) acid hydrolysis for optimized chromatographic performance of the XTerra Phenyl column is investigated. The XTerra Phenyl column showed the best separation of the less polar major metabolic oxidation products pentamethylphosphoramide and hydroxymethyl-pentamethylphosphoramide, however, only after treating the column with formic acid (acid-treated). The XTerra column separated most of the investigated HMPA oxidation products (11 of 16 compounds) in a single chromatographic run. In contrast, the XBridge Phenyl column requires one method for the less polar and another method for the more polar oxidation products. However, this results in an overall better separation performance of the XBridge Phenyl column, especially for the less polar major abiotic oxidation products hydroxymethyl-pentamethylphosphoramide and formyl-pentamethylphosphoramide, as well as for 11 highly polar oxidation products (R(S)>1.5). The RPLC/ESI-TOF-MS method presented and validated in this study is the first analytical method that can be used to separate and detect HMPA (LOD 0.10 μM without preconcentration) and all of its oxidation products.     

A validated chromatographic method for the determination of flavonoids in Copaifera langsdorffii by HPLC

Hydroethanolic extracts of C. langsdorffii leaves have therapeutic potential. This work reports a validated chromatographic method for the quantification of polar compounds in the hydroethanolic extract of C. langsdorffii leaves. A reliable HPLC method was developed using two monolithic columns linked in series (100 x 4.6 mm - C18), with nonlinear gradient elution, and UV detection set at 257 nm. A procedure for the extraction of flavonols was also developed, which involved the use of 70% aqueous ethanol and the addition of benzophenone as the internal standard. The developed method led to a good detection response as the values for linearity were between 10.3 and 1000 microg/mL, and those for recovery between 84.2 and 111.1%. The detection limit ranged from 0.02 to 1.70 microg/mL and the quantitation limit from 0.07 to 5.1 microg/mL, with a maximum RSD of 5.24%. Five compounds, rutin, quercetin-3-O-alpha-L-rhamnopyranoside, kaempferol-3-O-alpha-L-rhamnopyranoside, quercetin and kaempferol, were quantified. This method could, therefore, be used for the quality control of hydroethanolic extracts of Copaifera leaves and their cosmetic and pharmaceutical products.     

Amperometric Enzyme Biosensor Based on the Controlled Pore Glass

Abstract

A new amperometric biosensor based of glucose oxidase immobilized in aminopropyl-controlled pore glass (CPG) is reported. The glucose oxidase was linked to the CPG by covalent bonds with glutaraldehyde. The effect of analytical variables on the biosensor response was studied using experimental design methodology. Analytical properties such as linearity, detection limit, quantitation limit, range, and precision are reported. Interferences caused by compounds usually present in biological samples were eliminated.