在线自发电源激发的流动注射电致化学发光测定异烟肼

采用了一种与流动注射体系组合的在线自发电池作为电致化学发光的激发源（ 简称FI－GCECL）。实验发现在碱性介质中，Al/Ag双金属对可以提供稳定的电位输 出并可激发鲁米诺在铂电极表面的电致化学发光。此自发电池具有使用寿命长、电 位可由碱性介质组成调节、可组合到流动注射体系中等特点，利用这种组合体系， 检测了三家厂生产的片剂中的异烟肼含量，将结果与药典标准方法进行了比较，证 明了这种电致发光分析的可行性。     

流动注射后化学发光法测定异烟肼

本文发现了异烟肼在铁氰化钾-钙黄绿素化学发光反应体系中的后化学发光反应。优化了反应条件,建立了一种利用后化学发光反应测定异烟肼的流动注射化学发光分析法。方法的检出限为6×10-8g/mL, 相对标准偏差为1.8% (2.0×10-6 g/mL 异烟肼,n=11）,线性范围为2.0×10-7~1.0×10-5 g/mL。此法已用于异烟肼片剂中异烟肼含量的测定,结果与药典方法测定值一致。     

Flow-injection system for automated dissolution testing of isoniazid tablets with chemiluminescence detection

A simple and sensitive flow-injection chemiluminescence (CL) system for automated dissolution testing is described and evaluated for monitoring of dissolution profiles of isoniazid tablets. The undissolved suspended particles in the dissolved solution were eliminated via on-line filter. The novel CL system of KIO(4)-isoniazid was also investigated. The sampling frequency of the system was 120 h(-1). The dissolution profiles of isoniazid fast-release tablets from three sources were determined, which demonstrates the stability, great sensitivity, large dynamic measuring range and robustness of the system.     

纳米金-曙红Y体系荧光增强法检测异烟肼

基于异烟肼对纳米金-曙红Y体系的荧光增强作用,通过测定加入异烟肼前后体系荧光信号变化与异烟肼含量的关系,建立测定异烟肼的荧光分析方法.并探讨了实验机理,在优化的实验条件下,方法的线性范围为0.02～2.0 μg/mL,检出限为9 ng/mL.对异烟肼片中异烟肼含量进行了测定,测定值与标识值没有显著差异,加标回收率在96...     

Coulometric titration of benzoic and isonicotinic acid derivatives of hydrazides and acylhydrazones

It was found that benzoic acid hydrazides rapidly and quantitatively react with electrogenerated chlorine and bromine under the conditions of galvanostatic coulometry. Benzoic acid hydrazides were determined in model solutions. A good precision (RSD varied from 1 to 6%) allowed coulometry to be applied to the determination of isonicotinic acid hydrazide in isoniazid tablets and isonicotinic acid 3-methoxy-4-hydroxybenzylidenehydrazide in phthivazid tablets.     

Genetic Algorithm Based Potential Selection in Simultaneous Voltammetric Determination of Isoniazid and Hydrazine by Using Partial Least Squares (PLS) and Artificial Neural Networks (ANNs)

The voltammetric behavior of isoniazid and hydrazine at an overoxidized polypyrrole modified glassy carbon electrode has been investigated. The obtained cyclic voltammograms showed that their oxidation peaks were overlapped and it is difficult to determine them individually from a mixture without separation. To overcome this limitation, a procedure was proposed for resolution of overlapped voltammetric signals from mixtures of isoniazid and hydrazine. In this procedure, genetic algorithm was used for the selection of potentials for partial least squares. A feed forward artificial neural network with back propagation error algorithm was used to process the nonlinear relationship between currents and concentrations of hydrazine and isoniazid. The proposed method was suitable for determination of isoniazid in pharmaceutical tablets and detection of hydrazine impurities in the same samples.     

Indirect potentiometric determination of hydrazine, isoniazid, sulphide and thiosulphate with a chloramine-T ion-selective electrode

Indirect potentiometric procedures with chloramine-T (CAT) as the oxidant and a chloramine-T ion-selective electrode are described for the determination of hydrazine and isonicotinic acid hydrazide (isoniazid) in the 1-100 mumole range and of sulphide and thiosulphate in the 0.5-50 mumole range. The reductants react stoichiometrically with a known and excessive volume of added CAT and the unconsumed excess of CAT is measured with the CAT-selective electrode. Aqueous solutions of the reductants were analysed with an error and precision of about 1-2%. Analytical recovery of isoniazid added to tablet diluents was 97-101% (average 98.9%). Results were comparable with those obtained with a titrimetric method for the determination of isoniazid in injection solutions and tablets.     

HPLC–MS Analysis of Isoniazid in Dog Plasma

A simple, rapid, and sensitive liquid chromatography–mass spectrometric (LC–MS) method was developed and validated for the determination of isoniazid in dog plasma. Plasma samples were deproteined with methanol and separated on a C₁₈ column interfaced with a single quadrupole mass spectrometer, using 0.1% formic acid–acetonitrile (91:9 v/v) as mobile phase. Detection was performed by positive electrospray ionization with selected ion monitoring at m/z 138 for isoniazid and 152 for entecavir maleate internal standard. Linearity was obtained over the range of 25–5,000 ng mL^?1, with a lower limit of quantification of 25 ng mL^?1. The intra- and inter-day precision was less than 2.7% in terms of relative standard deviation. Accuracy, expressed as relative error, ranged from ?2.0 to 8.0%. Plasma samples were analysed within 5 min. The method was successfully applied to the evaluation of the pharmacokinetics of isoniazid in dog plasma.     

Voltammetric assay of rifampicin and isoniazid drugs, separately and combined in bulk, pharmaceutical formulations and human serum at a carbon paste electrode

The electrochemical oxidation of both the rifampicin (RIF) and isoniazid (INH) drugs has been investigated by cyclic and square-wave voltammetry in Britton-Robinson buffers (pH 2-11) at a carbon paste electrode. The oxidation of rifampicin generated a well-defined pH-dependent quasi-reversible anodic-cathodic peak couple corresponding to a mechanism involving the transfer of two electrons/two protons, typical to that of hydroquinones, in addition to an irreversible anodic peak at a more positive potential which may be due to the oxidation of phenolic hydroxyl group. For the isoniazid, an irreversible anodic peak was observed, which may be attributed to the irreversible oxidation of the amide moiety of the drug molecule. A validated square-wave adsorptive anodic stripping voltammetric procedure was described to assay the two drugs separately or combined in pharmaceutical formulations and human serum. The recoveries of RIF in rimactane^® capsules (300 mg RIF) and INH in isocid^® tablets (200 mg INH) were found to be 98.57±0.81% and 100.57±0.74%, respectively. The proposed procedure was also successfully applied to simultaneous assay of rifampicin and isoniazid drugs combined in rimactazid tablets (150 mg INH+300 mg RIF) with recoveries of 98.79±0.97% and 99.54±0.74%, respectively, without the necessity for sample pretreatment or time-consuming extraction steps prior to the analysis. The results were favorably compared to those obtained by the reported USP method. Moreover, the proposed procedure was successfully applied to simultaneous assay of both drugs in human serum samples with limits of detection and quantitation of 5×10⁻⁸ and 1.7×10⁻⁷ M for RIF and 6.1×10⁻⁸ and 2×10⁻⁷ M for INH.     

Spectrophotometric Study of Isoniazid by Using 1,2‐Naphthoquinone‐4‐Sulfonic Acid Sodium as the Chemical Derivative Chromogenic Reagent

A new method for the determination of isoniazid by using 1,2‐naphthoquinone‐4‐sulfonic sodium as the chemical derivative chromogenic reagent is established. The method is based on a condensation reaction to measure the pink compound produced by the reaction of isoniazid with 1,2‐naphthoquinone‐4‐sulfonic sodium in pH 13.00 buffer solution. The stoichiometric ratio of the compound is 1:1, and its maximum absorption wavelength is at 460 nm, ? = 1.18 × 10⁴ L·mol^?1 cm^?1. Beer's law is perfectly obeyed in the range of 0.50?30 μg.mL^?1 of isoniazid. The linear regression equation is A = 0.0185 + 0.11056C (mol.L^?1), with 0.9994 of a linear regression correlation. The detection limit is 0.40 μg.mL^?1, RSD is 0.48%, and average recovery is over 99.3%. This paper further optimizes the determination of isoniazid compared to the previous methods, and the kinetic property and reaction mechanism are studied intensively. This proposed method has been successfully applied to the determination of isoniazid in tablets of isoniazid with satisfactory results.     

Simultaneous Analysis of Isoniazid and Its Impurities by CZE

An alternative methodology for simultaneous determination of isoniazid, isonicotinic acid, 4-cyanopyridine, ethyl isonicotinate and isonicotinamide by capillary zone electrophoresis, within an analysis time of 11 min, is proposed. An electrolyte composed by 50 mmol L⁻¹ of acetic acid/sodium acetate buffer and 12.5 mmol L⁻¹ of Cu²⁺, an analyte dilution in 1 mmol L⁻¹ of Brij 35 and 12.5 mmol L⁻¹ of Cu²⁺ and +20 kV voltage were optimized. After evaluating some figures of merit, such as linearity, precision, recovery and quantification limit, the method was successfully applied to the isoniazid analysis in tablets. The contents found were 99.3 mg of isoniazid and 0.3 mg of isonicotinic acid, corresponding to 0.3 % of impurity regarding the content of the active ingredient in the pharmaceutical formulation.

     

Evaluation of a novel composite based on functionalized multi-walled carbon nanotube and iron phthalocyanine for electroanalytical determination of isoniazid

A novel platform for electroanalysis of isoniazid based on graphene-functionalized multi-walled carbon nanotube as support for iron phthalocyanine (FePc/f-MWCNT) has been developed. The FePc/f-MWCNT composite has been dropped on glassy carbon forming FePc/f-MWCNT/GC electrode, which is sensible for isoniazid, decreasing substantially its oxidation potential to +200 mV vs Ag/AgCl. Electrochemical and electroanalytical properties of the FePc/f-MWCNT/GC-modified electrode were investigated by cyclic voltammetry, electrochemical impedance spectroscopy, scanning electrochemical microscopy, and amperometry. The sensor presents better performance in 0.1 mol L^?1 phosphate buffer at pH 7.4. Under optimized conditions, a linear response range from 5 to 476 μmol L^?1 was obtained with a limit of detection and sensitivity of 0.56 μmol L^?1 and 0.023 μA L μmol^?1, respectively. The relative standard deviation for 10 determinations of 100 μmol L^?1 isoniazid was 2.5%. The sensor was successfully applied for isoniazid selective determination in simulated body fluids.     

The thermometric determination of isonicotinic acid hydrazide in isoniazid tablets

The determination of isonicotinic acid hydrazide in the dosage form of isoniazid tablets is done using thermometric titrimetry. The hydrazide is oxidized by hexacyanoferrate(III) ions. It is not necessary to separate the active ingredients from the powdered sample. The results from the proposed method are compared with those obtained using the standard B.P. method.     

Determination of isoniazid among pharmaceutical samples and the patients’ saliva samples by using potassium ferricyanide as spectroscopic probe reagent

A novel method to determine isoniazid with high sensitivity and good selectivity has been established by using potassium ferricyanide as spectroscopic probe reagent. In the presence of potassium ferricyanide, it has been demonstrated that iron(III) is reduced to iron(II) by isoniazid at pH 4.0. In addition, the in situ formed iron(II) reacts with potassium ferricyanide to give soluble prussian blue. The absorbance of soluble prussian blue is measured at the absorption maximum of 735 nm, and the amount of isoniazid can be calculated based on this absorbance. A good linear relationship of the concentration of isoniazid versus absorbance is observed with a linear range of 0.040-8.00 μg mL⁻¹. The linear regression equation is A = −0.00286 + 0.28588C (μg mL⁻¹) with a correlation coefficient of 0.9992. The detection limit (3σ/k) is 0.037 μg mL⁻¹, and its relative standard deviation (R.S.D.) is 0.35% (n = 11). Moreover, the apparent molar absorption coefficient of indirect determination of isoniazid is 3.92 × 10⁴ L mol⁻¹ cm⁻¹. The parameters with regard to determination are optimized, and the reaction mechanism is discussed. This method has been successfully applied to the determination of isoniazid in pharmaceutical samples and saliva samples of patients.     

Spectroscopic studies of isonicotinoyl-, nicotinoyl-, and piconoylhydrazines with chloranil

Isonicotinoyl-, nicotinoyl-, and piconoylhydrazines form molecular complexes with chloranil at pH 9. The composition and stability of these complexes have been studied spectrophotometrically. The results indicate that all complexes were of the 1:1 type and their stabilities depend on the position of the substituent group in the pyridine ring. The method of complexation was used to determine parts per million amounts of INH, NH, PH, and isoniazid tablets in solution spectrophotometrically.     

Tailoring Atomoxetine Release Rate from DLP 3D-Printed Tablets Using Artificial Neural Networks: Influence of Tablet Thickness and Drug Loading

Various three-dimensional printing (3DP) technologies have been investigated so far in relation to their potential to produce customizable medicines and medical devices. The aim of this study was to examine the possibility of tailoring drug release rates from immediate to prolonged release by varying the tablet thickness and the drug loading, as well as to develop artificial neural network (ANN) predictive models for atomoxetine (ATH) release rate from DLP 3D-printed tablets. Photoreactive mixtures were comprised of poly(ethylene glycol) diacrylate (PEGDA) and poly(ethylene glycol) 400 in a constant ratio of 3:1, water, photoinitiator and ATH as a model drug whose content was varied from 5% to 20% (w/w). Designed 3D models of cylindrical shape tablets were of constant diameter, but different thickness. A series of tablets with doses ranging from 2.06 mg to 37.48 mg, exhibiting immediate- and modified-release profiles were successfully fabricated, confirming the potential of this technology in manufacturing dosage forms on demand, with the possibility to adjust the dose and release behavior by varying drug loading and dimensions of tablets. DSC (differential scanning calorimetry), XRPD (X-ray powder diffraction) and microscopic analysis showed that ATH remained in a crystalline form in tablets, while FTIR spectroscopy confirmed that no interactions occurred between ATH and polymers.     

hGH release from directly compressed hGH-PLGA biodegradable implantable tablets: Influence of physicomechanical factors

The incidence of compression conditions, porosity and polymer degradation on human growth hormone (hGH) release from PLGA implantable tablets was evaluated with the aim of gaining insight in the mechanism involved in drug delivery from biodegradable matrices. Tablets elaborated by direct compression of hGH with PLGA, applying various compression forces for different times, kept the integrity and the stability of the hormone. Tablet dimensions, viscoelastic properties, glass to rubber transition temperature (T_g), PLGA degradation rate and water uptake were analyzed in the freshly prepared implantable tablets as well as at several times during release test in phosphate buffer pH 7.4. Placebo tablets were also prepared to evaluate the incidence of hGH on the physicomechanical properties of the device and PLGA degradation rate. Porosity remarkably determined the amount of hGH released, through an effect on the easiness of water penetration in the tablet and on the beginning of PLGA degradation. The decrease in PLGA molecular weight during the first days in the release medium, despite of being minor, significantly conditioned hGH release rate. The more dramatic changes in PLGA molecular weight observed after 20 days in the release medium notably reduced the T_g and the viscous and elastic moduli of the tablets. The overall analysis of the events underwent by the tablets in contact with the aqueous medium was used to explain the drug release profile and may help to optimize the design of the PLGA-based implantable tablets as peptidic drug delivery systems.     

Ternary mutual diffusion of isoniazid in aqueous sodium chloride,sodium hydroxide,and hydrochloric acid at T = 298.15 K

Ternary mutual diffusion coefficients measured by Taylor dispersion method (D₁₁, D₂₂, D₁₂, and D₂₁) are reported for aqueous solutions containing isoniazid and different electrolytes (NaCl, NaOH, or HCl) at T = 298.15 K at different carrier concentrations. These diffusion coefficients have been measured having in mind a better understanding of the structure of these systems and the thermodynamic behaviour of isoniazid in different media. For example, it is possible to make conclusions about the influence of these electrolytes in diffusion of isoniazid, and to obtain information concerning the number of moles of each component transported per mole of the other component driven by its own concentration gradient.     

Development of an on-site screening system for amphetamine-type stimulant tablets with a portable attenuated total reflection Fourier transform infrared spectrometer

We tried to develop a library search system using a portable, attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectrometer for on-site identification of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) tablets. The library consisted of the spectra from mixtures of controlled drugs (e.g. MDMA and ketamine), adulterants (e.g. caffeine), and diluents (e.g. lactose). In the seven library search algorithms, the derivative correlation coefficient showed the best discriminant capability. This was enhanced by segmentation of the search area. The optimized search algorithm was validated by the positive (n = 154, e.g. the standard mixtures containing the controlled drug, and the MDMA/MDA tablets confiscated) and negative samples (n = 56, e.g. medicinal tablets). All validation samples except for four were judged truly. Final criteria for positive identification were decided on the basis of the results of the validation. In conclusion, a portable ATR-FT-IR spectrometer with our library search system would be a useful tool for on-site identification of amphetamine-type stimulant tablets.     

反相高效液相法测定血浆及尿液中的异烟肼

 建立了血浆及尿液中异烟肼的高效液相快速测定方法 ,以满足临床药物分析和法医学鉴定的需要 ,提高对血浆及尿液中异烟肼浓度检测的准确性。以香草醛为衍生化试剂 ,将异烟肼经柱前衍生为异烟肼 香草醛腙 ,直接对处理后样品中的腙进行定性、定量分析。以在空白人体液样本中定量添加标准异烟肼的方法考察了样品的前处理方法、仪器条件、线性范围、精密度、回收率等 ,并对健康受试者血液中的异烟肼浓度进行了监测。结果表明 ,方法的线性范围为 0 2mg/L～ 1 2 0mg/L ;检测限为 0 2mg/L ;日内、日间精度均小于 4 0 % (n =5) ;回收率在96 3 %以上。