Determination of pipemidic acid based on flow-injection chemiluminescence due to energy transfer from peroxynitrous acid synthesized on-line

A flow-injection chemiluminescence (CL) method for the determination of pipemidic acid is described. It is based on energy transfer from excited state peroxynitrous acid to pipemidic acid, in which the excited state peroxynitrous acid is synthesized on-line by the mixing of acid hydrogen peroxide with nitrite in a flow system and the CL is from two excited states of pipemidic acid. The proposed method allows the measurement of pipemidic acid over the range of 2.0×10^–7–2.0×10^–5 mol l^–1 . The detection limit is 6.3×10^–8 mol l^–1, and the relative standard deviation for 2.0×10^–6 mol l^–1 pipemidic acid (n= 9) is 0.9%. This method was evaluated by the analysis of pipemidic acid in pharmaceutical preparations.     

Complexation Study and Spectrofluorimetric Determination of Pipemidic Acid with γ-Cyclodextrin

The fluorimetric characteristics of pipemidic acid (PIPE) have been investigated. It has been proven that the fluorescence emission band of pipemidic acid at 439 nm is significantly intensified in the presence of γ-cyclodextrin. The inclusional complexation between the antibacterial pipemidic acid and γ-cyclodextrin (γ-CD) has been studied. A 1:1 stoichiometry of the complex was established and its association constant was calculated by a nonlinear regression method, monitoring the changes in the fluorescence signal of pipemidic acid in the presence of γ-CD. According to the results obtained, a spectrofluorimetric method for the determination of PIPE has been proposed. The best limits of detection and quantification were obtained in presence of γ-CD, in acidic media. The dynamic range of the method was comprised between 0.18 and 1.40 μg/ml.     

Flow Injection Chemiluminescence Determination of Pipemidic Acid Using On-Line Electrogenerated Cobalt(III) as Oxidant

 A novel flow injection chemiluminescence (CL) system for the determinati on of pipemidic acid is described. It is based on the direct CL reaction of pipemidic acid and Co(III) in acid medium. The unstable Co(III) was on-line electrogenerated by constant current electrolysis. The CL intensity was linear with pipemidic acid concentration in the range of 0.01∼100 μg/ml, the determination limit was 3.3×10⁻⁹ g/mL. The whole process could be complete d in 1 min with a relative standard deviation of 3.2%. The proposed method is suitable for automatic and continuous analysis and has been applied successfully to the analysis of pipemidic acid in a pharmaceutical preparation. Received November 22, 1999. Revision March 24, 2000.     

Chemiluminescence flow-through sensor for pipemidic acid using solid sodium bismuthate as an oxidant

A novel chemiluminscence (CL) flow-through sensor for pipemidic acid is described. It was based on the sensitizing effect of pipemidic acid on the CL oxidation of sulfite by sodium bismuthate in H₂SO₄ media. The solid-phase sodium bismuthate was mechanicially immobilized on the sponge rubber inside of the CL flow cell as CL oxidant. The calibration graph is linear in the range 0.1-10 μg/ml with a detection limit of 6.2×10⁻⁸ g/ml (3σ). A complete analysis could be performed in 1 min with a relative standard deviation (R.S.D.) of 2.5% for 2 μg/ml pipemidic acid (n=8). This method has been successfully applied to determine pipemidic acid in pharmaceutical preparation.     

Flow-injection chemiluminescence detection for studying protein binding for drug with ultrafiltration sampling

The novel flow chemiluminescence (CL) system for determination of pipemidic acid was proposed, which was based on the sensitizing effect of pipemidic acid on the CL oxidation of sulfite by KMnO₄ in acid media. Combined with the technique of ultrafiltration, the flow-injection CL system was applied to study in vitro the bovine serum album (BSA) binding of pipemidic acid. The estimated association constant (K) and the number of the binding site (n) on one molecule of BSA were 8.81×10⁴ l/mol and 0.94, respectively. The method provided a fast and simple technique for the study of drug-protein interaction.     

吡哌酸分子印迹聚合物的分子识别

采用分子印迹技术合成了吡哌酸分子印迹聚合物。运用平衡结合实验研究了聚合物的吸附特性和选择性识别能力。Scatchard分析表明,在本文所研究的浓度范围内,聚合物中形成了两类不同的结合位点。吡哌酸分子印迹聚合物对吡哌酸呈现较高的选择识别特性,可作为固相萃取剂,在人血清吡哌酸的分析中对样品进行了有效的提取和净化。     

Homogeneous chemiluminescence system in neutral and near neutral aqueous solution with ClO2 as oxidant and its analytical application

Using ClO₂ as chemiluminescence (CL) oxidant, a novel homogeneous CL system in neutral and near neutral aqueous solution is proposed in this paper. ClO₂ could oxidize sulfite in pH 5.0–8.5 acetate buffer to produce CL emission, and pipemidic acid could sensitize the CL system. The ClO₂–SO₃²⁻–pipemidic acid reaction was used as a model CL system and explored the possibility of highly active and eco-friendly ClO₂ being used as CL oxidant in neutral and near neutral aqueous solution. Combined with flow-injection analysis, the proposed CL system was applied to the automated dissolution testing of pipemidic acid tablet. Compared with the common strong acidic or strong basic CL system, this proposed CL owns its advantages.     

Spectrophotometric Determination of Some Antibacterial Drugs Using p-Nitrophenol

Abstract

A simple, quick and sensitive spectrophotometric method for pipemidic acid, norfloxacin and ciprofloxacin lactate is described, based on a reaction with p-nitrophenol in water medium, apparently by a charge-transfer mechanism, to yield 1:1 complexes with analytically useful maximum absorption at 404 nm, 407nm and 403nm. Optimum conditions for determination, linear calibration range and apparent molar absorptivities have been reported. The methods are highly accurate and have been successfully applied to the determination of pipemidic acid, norfloxacin and ciprofloxacin lactate in tablets. The results are in good agreement with the official methods.     

Determination of Selected Quinolones and Fluoroquinolones by Use of TLC

Abstract

There are many different methods of quinolones determination. The most often used method of quinolones analysis is liquid chromatography. In this work some selected quinolones (cinoxacin, pipemidic acid) and fluoroquinolones (ofloxacin, pefloxacin) were separated with thin-layer chromatography (TLC). The two different mobile phases were used as follows: buffer solution (pH = 5.5)-methanol, 40:10 (v/v) and acetonitrile-water-acetic acid, 6:40:4 (v/v/v), respectively, for quinolones and fluoroquinolones. The following chromatographic parameters were calculated for these separations: R_F, ?R_F, R_M, and R_S. The possibility of qualitative determination of cinoxacin, pipemidic acid, ofloxacin, and pefloxacin using TLC was shown.     

Complexation of antibacterial quinolonic acid and cinolonic derivatives with Zn(II) and Al(III): application to their determination in human urine

Nalidixic acid, 7-hydroxymethylnalidixic acid, oxolinic acid, pipemidic acid and cinoxacine form complexes with zinc(II) in the presence of acetate buffer of pH 5.5 and oxolinic acid, pipemidic acid and cinoxacine form complexes with aluminium(III) in the presence of chloroacetate buffer of pH 3.0. In all cases, an enhancement of the fluorescence emission was observed. Fluorimetric studies on the spectral characteristics of the complexes were performed. A 1:1 stoichiometry for all the complexes was established. The association constants were calculated, by using the changes in the fluorescence of all antibacterials, that occurred when the complexes were formed. The fluorescence reactions were used to develop methods for the determination of all of the above compounds, showing a higher sensitivity than in the absence of the cationic ions. The methods were satisfactorily applied to the determination of these compounds in urine.     

Phototoxic potential of quinolones.

The photohaemolytic potentials of the quinolones oxolinic acid, pipemidic acid, rosoxacin, norfloxacin, ciprofloxacin and M-193324 (synthesis intermediary) were evaluated and compared with the photohaemolysis induced by nalidixic acid. Quinolones with a piperazine group in position 7 (pipemidic acid, norfloxacin and ciprofloxacin) did not induce photohaemolysis. However, oxolinic acid, rosoxacin and M-193324 produced a concentration- and oxygen-dependent photohaemolysis. Ascorbic acid, histidine and thiourea inhibited the photohaemolysis induced by oxolinic acid, rosoxacin and M-193324, suggesting a photodynamic mechanism similar to that found with nalidixic acid. In addition, deuterium oxide increased the photohaemolysis induced by photohaemolytic quinolones, indicating that this process is mediated by singlet oxygen.     

A new method of quantification of pipemidic-acid by capillary zone electrophoresis with end-column amperometric detection

Capillary zone electrophoresis was employed for the determination of pipemidic acid using an end-column amperometric detection with a carbon fiber microdisk array electrode, at a constant potential of -1.10 V vs. saturated calomel electrode. The optimum conditions of separation and detection were 1.2 x 10(-4) mol/LNaOAc - 8.8 x 10(-4) mol/ LHOAc for the buffer solution, 20 kV for the separation voltage, 5 kV and 10 s for the injection voltage and the injection time. The limit of detection was 1.05 x 10(-7) mol/L or 189 amol (S/N=3). The relative standard deviation was 0.31% for the migration time and 2.0% for the electrophoretic peak current. The method was applied to determining pipemidic acid in human serum.     

Dispersive liquid–liquid microextraction combined with nonaqueous capillary electrophoresis for the determination of fluoroquinolone antibiotics in waters

Dispersive liquid–liquid microextraction (DLLME) was combined for the first time with NACE‐UV for the selective determination of eight fluoroquinolone antibiotics (lomefloxacin, levofloxacin, marbofloxacin, ciprofloxacin, sarafloxacin, enrofloxacin, danofloxacin and difloxacin) in mineral and run‐off waters. Field‐enhanced sample injection was carried out in order to improve the sensitivity, whereas pipemidic acid was used as internal standard. The BGE that provided complete separation of the eight analytes and the internal standard was composed of 3 M acetic acid, 49 mM ammonium acetate in 55:45 v/v methanol:ACN. Optimum DLLME conditions (extraction of 5 mL of water at pH 7.6 with 685 μL of CHCl₃ and 1250 μL of ACN, extractant and disperser solvents, respectively) were achieved by means of experimental design methodology. Calibration curves of the whole method were obtained with correlation coefficients (R) higher than 0.994 in all cases. An accuracy and precision study was carried out at different levels of concentration, finding that there were no significant differences (Student's t‐test) between real and spiked concentrations.     

Assembly of an unprecedented metal-pipemidic acid complex modifying octamolybdates containing like DNA spiral chain

By introducing antibacterial drugs pipemidic acid into the octamolybdates, an unprecedented compound, [Zn(PPA)₂(H₂O)]₂·[Mo₈O₂₆]·3.5H₂O (1) (PPA = pipemidic acid), has been synthesized and characterized by routine physical methods. Single-crystal X-ray diffraction analysis reveals that the title compound contains the right- and left-double-stranded like DNA helical chains, which are assembled together via sharing the β-Mo₈ clusters forming the fascinating double intertwined inverted helices. The result of the antitumor activities shows that the title compound possesses higher antitumor activity and selectivity.     

交流示波极谱滴定法测定吡哌酸

本文介绍用交流示波极谱滴定法测定吡哌酸的含量。在ＨＣｌ－ＮａＡｃ缓冲溶液中，加入过量的Ｎａ－ＴＰＢ与吡哌酸作用生成沉淀，过滤后用亚铊标准溶液定滤液中过量的ＴＰＢ，由交流示波极谱图上ＴＰＢ的切口消失指示终点。本法操作简便，终点直观，应用于原料药样品的测定，并与药典法相对照，结果基本吻合。     

The influence of chitosan on in vitro properties of Eudragit RS microspheres

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.     

Polarographische Gehaltsbestimmung von Pipemids?ure in Kapseln

Ohne Zusammenfassung

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Polarographic determination of pipemidic acid in capsules

     

Simultaneous determination of quinolones in fish by liquid chromatography coupled with fluorescence detection: Comparison of sub‐2 μm particles and conventional C18 columns

A simple and effective multi‐residue analysis method is presented for the extraction and determination of eleven quinolones (pipemidic acid, enoxacin, norfloxacin, ciprofloxacin, lomefloxacin, enrofloxacin, gatifloxacin, difloxacin, oxolinic acid, nalidixic acid and flumequine) in fish tissues. In this study, multi‐residue separations on four columns packed with 5 μm or sub‐2 μm particles were simultaneously developed for the purpose of comparison. Various gradients were optimized and best resolutions were achieved on each column. A short and sub‐2 μm particle‐sized HPLC column was chosen for its advantages in analysis time and column performance. Additionally, considering the matrix effect of the complex crude fish tissue, an effective extraction protocol was also established for sample pre‐treatment procedure. Good recoveries (71–98%) were obtained from samples fortified with a mix of eleven quinolones at three levels, with satisfactory relative standard deviations and limits of detection. As a result, the sub‐2 μm HPLC column and proposed analytical procedures have been evaluated and applied to the analysis of different fish tissues. Detectable residues were observed in 8 of 30 samples, at concentrations ranging from 4.74 to 23.27 μg/kg.     

Determination of quinolone residues in chicken and fish by capillary electrophoresis-mass spectrometry

A specific pressure-assisted CE-MS method is described for the analysis of five quinolone residues. MS using a single quadrupole is compared with multiple-stage MS using a quadrupole IT (QIT-MS(n)). The procedure involves a common sample preparation by SPE on disposable cartridges. The most suitable electrolyte is 60 mM (NH(4))(2)CO(3) at pH 9.2. Single quadrupole does not provide enough fragmentation to confirm identities according to the current legislation. However, QIT-MS(n) achieves selective fragmentation. Using this method, danofloxacin, enrofloxacin, flumequine, ofloxacin, and pipemidic acid are analyzed in fortified samples of chicken and fish. Recoveries at levels of 50 ng/g were 62-99%, except for flumequine, which gives recoveries > or =45%. RSDs are from 9 to 16% and the LOD is equal (20 ng/g) for the five analytes. Confirmation of the quinolones' identity is achieved using QIT-MS(3). Forty samples of chicken and fish taken from different local markets are analyzed. Enrofloxacin is also determined in incurred chicken muscle using this method.     

高效液相色谱-串联质谱法测定蜂蜜中残留的19种喹诺酮类药物

建立了高效液相色谱-电喷雾串联质谱联用测定蜂蜜中恩诺沙星、环丙沙星、诺氟沙星、氧氟沙星、双氟沙星、恶喹酸、氟甲喹、沙拉沙星、司帕沙星、丹诺沙星、氟罗沙星、马波沙星、伊诺沙星、奥比沙星、吡哌酸、培氟沙星、洛美沙星、西诺沙星和萘啶酸等19种喹诺酮类药物残留的方法。比较酸性溶液阳离子固相萃取(PCX柱)、近中性缓冲溶液反相固相萃取（HLB柱）和碱性溶液阴离子固相萃取(PAX柱)3种不同提取净化方法的提取效果,最终选择使用碱性溶液溶解蜂蜜样品,强阴离子固相萃取柱一步富集净化。以甲醇和0.1%甲酸溶液作为流动相,C18作为分析色谱柱,采用梯度洗脱方式进行液相色谱分离,选择离子反应监测模式检测19种喹诺酮类药物,内标方法定量。在1～100 μg/L范围内,19种喹诺酮类药物的线性相关系数均大于0.991。通过实际样品的添加回收试验,方法的定量限（S/N=10）为1.0 μg/kg,3个添加水平的回收率为71%～118%,相对标准偏差为4.2%～6.7%。