Spectrophotometric Determination of Lisinopril in Pure and Pharmaceutical Formulations

An accurate, simple, fast, and cheap spectrophotometric method has been developed for the determination of lisinopril in pharmaceutical pure and dosage forms. The method is based on the reaction of ninhydrin with primary amine present in the lisinopril in the presence of DMF. This reaction produces a greenish blue colored product which absorbs maximally at 600 nm. Beer's law was obeyed in the range of 10–150 μg/mL with molar absorptivity of 4.083 × 10³ L mole^?1 cm^?1. The effects of variables such as temperature, heating time, concentration of color producing reagent, and stability of color were investigated to optimize the procedure. The results are validated statistically. The proposed method was applied to commercially available tablets, and the results were statistically compared with the official potentiometric method.     

Polarographic Determination of Lisinopril in Pharmaceuticals and Biological Fluids Through Treatment with Nitrous Acid

 A simple and highly sensitive polarographic method was developed for the determination of lisinopril in dosage forms and biological fluids. The method is based on treatment of the compound with nitrous acid followed by measuring the cathodic current produced by the resulting nitroso derivative. The polarographic behavior was studied adopting direct current (DC_t), differential pulse (DP) and alternating current (AC_t) polarography. A well-defined, diffusion-controlled cathodic wave over the pH range of 1.0–8.0 was obtained in Britton-Robinson buffers (BRb). At pH 3.0, the value of limiting diffusion-current constant (K) was 8.42 ± 0.23 (n = 7). The limiting diffusion current-concentration relationship was found to be rectilinear over the range of 2–24 μg/mL and 0.1–20 μg/mL using DC_t and DP polarographic modes, respectively. The minimum detectability was (S/N = 2) 0.02 μg/mL (4.54 × 10⁻⁸ M). The proposed method was successfully applied to the determination of lisinopril either per se or in dosage forms and the results obtained were in good agreement with those given using a reference method. The proposed method was further applied to the determination of lisinopril in spiked human urine and plasma. The percentage recoveries adopting the DP polarographic mode were 99.71 ± 1.87 and 97.16 ± 1.09, respectively. Received October 18, 2001; accepted July 31, 2002     

Spectrophotometric Study on Kinetics of Solvatochromism of Methyl Violet in Aqueous Methanol

The kinetics of the reaction of methyl violet with iodide in aqueous methanol system was studied by spectrophotometric method. The rate of reaction of methyl violet in different alcoholic composition in presence of potassium iodide was observed at pH 4 and 6 at various temperatures (298–318 K). Solvatochromic effect was studied in different percentages of methanol (0–50%). Bathochromic shift was observed with the decrease in polarity of solvent. The color change was attributed to molecule's structure, the delocalization of unit electrical charge causes deepening of color and decrease of delocalization causes fading of color due to reduction of dye. Increase in the rate of reaction was observed with increase in alcoholic content and also affected by potassium iodide salt and increased with increase in concentration of potassium iodide. Energy of activation (E_a) and transition energy (E_T) were calculated with the help of kinetic data. Thermodynamic parameters such as enthalpy change of activation (ΔH*), Gibbs free energy change of activation (ΔG*) and entropy change of activation (ΔS*) were evaluated as a function of concentration of solvent and salt.     

Spectroscopic,conformational analysis,structural benchmarking,excited state dynamics,and the photovoltaic properties of Enalapril and Lisinopril

There have been numerous attempts to theoretically design a better photovoltaic property with much interest on how to improved absorption and emission parameters of most reactive compounds in respect to dye – sensitized solar cells (DSSCs). This is regardless of the promising futures of the photovoltaic properties. However, for such effective design, it is necessary to understand the electronic and photophysical properties of the dye systems. Herein detailed density functional theory (DFT) and time – dependent DFT (TD-DFT) investigation of the excited state characteristics and the influence of various solvents: water, acetone, ethanol and chloroform on the photophysical properties of enalapril and lisinopril were investigated along with the experimental spectral (UV–vis and FT-IR) analysis. The electronic structure calculations were conducted using the 6–311++G(d,p) basis set in combination with B3LYP, M06-2X, and ?B97XD DFT functionals for the structural benchmarking investigations of the studied compounds. Results of the excitation electronic analysis of enalapril was observed to have wavelength absorption in the order gas > chloroform > ethanol > water which correspond to 229.19, 228.81, 228.85, 229.03 nm respectively while Lisinopril have the order of chloroform > gas > water > ethanol which present ethanol have the highest transition energy. In all the studied structured, the transition assignment corresponds to π $\to$ π* all corresponding to the Frank -Condon local excitation. It can be inferred from the photovoltaic properties that among the studied compounds in four different phases enalapril have the highest oscillator strength, but the values of light-harvesting efficiency (LHE) varies and show greater stability in Lisinopril. Lisinopril was observed to have the highest value of $V_{OC}$ compared to Enalapril this further confirmed the result obtained from the frontier molecular orbitals.     

Activation energies for metastable to stable phase transition of 4,4'-di-n-heptyl- oxyazoxybenzene

Complexes of adenine, AdH, with cobalt, nickel and copper chlorides were prepared and their thermodynamic functions were determined. The complexing processes are endothermic in nature. The thermal behaviour of complexes was followed up by using TG and DTA analyses. The stoichiometry of thermal decomposition of the investigated complexes was suggested. This revised version was published online in August 2006 with corrections to the Cover Date.     

Validated Method for the Simultaneous Determination of Lisinopril,Pravastatin, Atorvastatin and Rosuvastatin in API,Formulations and Human Serum by RP‐HPLC

Lisinopril is found to be useful in hypertension and statins as cholesterol lowering drug. Present work was designed for the simultaneous determination of lisinopril in presence of pravastatin, atorvastatin, and rosuvastatin using RP‐HPLC method. A Purospher star C18 (5 μm, 25×0.46 cm) column was used with mobile phase consisting of acetonitrile:water (60:40 V/V, pH 3.0) with flow rate of 1.0 mL·min^?1 and the quantitative evaluation was performed at 225 nm. The retention time of lisinopril was 2.0 min and for pravastatin, rosuvastatin and atorvastatin was found to be 3.1, 4.5 and 8.3 min respectively. Suitability of this method for the quantitative determination of the drugs was proved by validation in accordance with the requirements laid down by International Conference on Harmonization (ICH) guidelines. Application of the suggested procedures were successfully applied to the determination of these compounds in active pharmaceutical ingredient and in pharmaceutical preparations, with high percentage of recovery, good accuracy and precision.     

Synthesis,characterization, speciation and biological studies on metal chelates of 1-benzoyl(1,2,4-triazol-3-yl)thiourea

Proton-ligand association constants of 1-benzoyl(1,2,4-triazol-3-yl)thiourea (BTTU) and its complex formation constants with some bivalent metal ions Ni(II), Co(II), Mn(II), Zn(II), and Cu(II), have been determined potentiometrically in 50% EtOH–H₂O and 0.1 M NaNO₃. The complexes formed in solution have a stoichiometry of 1:1 and 1:2 [M:L], where M represents the metal ion and L the BTTU ligand. The corresponding thermodynamic parameters are derived and discussed. The complexes are stabilized by enthalpy changes and the results suggest that complexation is an enthalpy-driven process. The effects of metal ion, ionic radius, electronegativity, and nature of ligand on the formation constants are discussed. The formation constants of the complexes with 3d transition metals follow the order Mn²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺ > Zn²⁺. The metal complexes were synthesized and characterized by elemental analyses, conductance, IR, ¹H NMR, and magnetic measurements. The low magnetic moment of 0.11 BM for the Cu(II) complex is suggestive of dimerization through Cu–Cu interaction. The concentration distribution diagrams of the complexes were evaluated. The ligands and their metal complexes have been screened in vitro against some bacteria and fungi.     

Kinetics and mechanism of solid state imidapril hydrochloride degradation and its degradation impurities identification

A detailed stability testing of solid state imidapril hydrochloride (IMD) was performed and its degradation products were identified. The analysis was conducted according to ICH guidelines Q1A(R2). Pure IMD samples were exposed to stress conditions of elevated temperature and relative humidity (T = 363 K, RH = 76.4%) in order to accelerate degradation. The regular loss of IMD content with time, and the formation of two degradation impurities were observed. The appropriate reaction rate constants k (for IMD degradation and for the formation of product I and II) were calculated using Prout-Tompkins equation. The obtained degradation products were separated and identified by means of LC-MS technique. Based on the obtained m/z values, the masses and the structures of the formed degradation impurities were established. Also IMD degradation scheme was constructed. It was demonstrated that under the applied analytical conditions, IMD degradation follows an autocatalytic reaction model with the rate constant k = (4.764 ± 0.34)×10 ^?6 s ^?1 and with the parallel formation of two degradation products: imidaprilat and the diketopiperazine derivative. The obtained experimental results are in agreement with IMD degradation pathways proposed theoretically.      

Kinetics of the complex process of thermo-oxidative degradation of poly(vinyl alcohol)

The thermo-oxidative degradation of poly(vinyl alcohol) (PVA) has been investigated by TG+DTG+DTA simultaneous analysis performed in static air atmosphere, at four heating rates, namely 3, 5, 10 and 15 K min⁻¹. TG, DTG and DTA curves showed that, in the temperature range 25–700°C, four successive processes occur. The first process consisting in the loss of physical adsorbed water is followed by three processes of thermal and/or thermo-oxidative degradations. The processing of the non-isothermal data corresponding to the second process (the first process of thermo-oxidation) was performed by using Netzsch Thermokinetics — A Software Module for Kinetic Analysis. The dependence of the activation energy evaluated by Friedman’s isoconversional method on the conversion degree shows that the investigated process is complex one. The mechanism of this process and the corresponding kinetic parameters were determined by Multivariate Non-linear Regression Program and checked for quasi-isothermal experimental data. It was pointed out that the first process of thermo-oxidation of PVA consists in three consecutive steps having Avrami-Erofeev kinetic model. The obtained results can be used for prediction of the thermal lifetime of PVA corresponding to a certain temperature of use and an endpoint criterion.     

Non-isothermal Dehydration Kinetics of Some Cationites

The kinetic parameters of dehydration were determined under non-isothermal conditions for different polystyrenedivinylbenzene sulfonic acid type cationites (DVB) and their dependence on the degree of cross-linking granulation, porosity, specific surface, content of SO₃M groups (M=Li, Na, K, Rb), nature of the alkali metal in partially neutralized -SO₃H groups and heating rate was investigated. This revised version was published online in July 2006 with corrections to the Cover Date.     

Photo-sensitized degradation of CCl4-doped polystyrene in the solid phase

The photo-degradation of carbon tetrachloride (CCl₄)-doped polystyrene film has been investigated by ultraviolet (uv) and Fourier transform infrared (FTIR) spectroscopic techniques and by gel and viscosity measurements. On photo-irradiation of CCl₄-doped polystyrene film, the amount of oxygenated products and unsaturation increased with the concentration of carbon tetrachloride up to 5 mol%. Changes in gel fraction and number of chain scissions showed a similar trend to those of the amount of oxygenated products and unsaturation. These experimental results show that the degradation of polystyrene is photo-sensitized by added carbon tetrachloride. A possible mechanism for the photo-degradation of CCl₄-doped polystyrene is proposed.     

Kinetics of solid phase thermal polycondensation of aspartic acid in evacuated system

Solid phase thermal polycondensation of aspartic acid in evacuated system results in formation of poly(aspartic acid) at 190–207°C and in poly(succinimide) at 210–230°C. Kinetic parameters of formation of poly(aspartic acid) and poly(succinimide) have been determined. The aspartic acid → poly(aspartic acid) → poly(succinimide) polycondensation is accompanied by partial decarboxylation of the monomeric units.     

Kinetics studies of the degradation of sirolimus in solid state and in liquid medium

The use of sirolimus and its analogs has been evaluated for the treatment of different cancer types. The stability studies of sirolimus enabled to determine the kinetics of its chemical reactions in solid state and in the liquid medium. During intrinsic stability tests in a liquid medium, sirolimus showed a lack of stability when exposed to heat, neutral and basic hydrolysis. Analysis by high-performance liquid chromatography detected: two degradation products after exposure to heat; one degradation product for both basic and neutral hydrolyses; and all degradation products exhibited UV spectra similar to the drug’s spectrum. Kinetics studies in a liquid medium revealed low drug stability in methanolic solution; this instability may be exacerbated in the presence of water or high pH. The application of solid-state kinetic models showed that the drug degrades in accordance with the diffusion dimensional model, with greater stability and an expiration date equal to 6 years, demonstrating that sirolimus has satisfactory stability in the solid state. Through this understanding, it is possible to develop more stable pharmaceutical formulations using sirolimus.

     

Kinetics of Reduction of Some Surfactant-Cobalt(III) Complexes by Iron(II)

The electron transfer kinetics of the reaction between the surfactant-cobalt(III) complex ions, cis-[Co(en)₂(C₁₂H₂₅NH₂)₂]³⁺, cis-α-[Co(trien)(C₁₂H₂₅NH₂)₂]³⁺(en:ethylenediamine, trien:triethylenetetramine, C₁₂H₂₅NH₂ : dodecylamine) by iron(II) in aqueous solution was studied at 298, 303, 308 K by spectrophotometry method under pseudo-first-order conditions using an excess of the reductant in self-micelles formed by the oxidant, cobalt(III) complex molecules, themselves. The rate constant of the electron transfer reaction depends on the initial concentration of the surfactant cobalt(III) complexes. ΔS^# also varies with initial concentration of the surfactant cobalt(III) complexes. By assuming outer-sphere mechanism, the results have been explained based on the presence of aggregated structures containing cobalt(III) complexes at the surface of the self-micelles formed by the surfactant cobalt(III) complexes in the reaction medium. The rate constant of each complex increases with initial concentration of one of the reactants surfactant-cobalt(III) complex, which shows that self micelles formed by surfactant-cobalt(III) complex itself has much influence on these reactions. The electron transfer reaction of the surfactant-cobalt(III) complexes was also carried out in a medium of various concentrations of β-cyclodextrin. β-cyclodextrin retarded the rate of the reaction.     

Role of Hansen solubility parameters in solid phase extraction

The sorbent–eluent systems combined from eight polymeric sorbents and seven solvents as eluents were used for the extraction of phenol and its oxidation products from water samples. The individual interactions between sorbents, eluents and analytes were characterized by Hansen solubility parameters. Principal components analysis (PCA) was used for revealing the dominant interactions (dispersive, polar, and hydrogen bonding type) in sorbent–analyte–eluent systems. The importance of solubility parameters was also determined by a novel procedure based on sum of ranking differences (SRD). Although PCA and ranking by SRD are based on different principles and calculations, they have provided very similar results. The recovery in a given system has been predicted from the magnitudes of mutual interactions (sorbent–analyte, sorbent–eluent, analyte–eluent) by multiple linear regression.     

Kinetics of hydrolysis of xylometazoline (XYL) in aqueous solution

The effect of pH (over the range of 2.10 - 11.90) and temperature (from 353 K to 363 K) on the stability of xylometazoline (XYL) has been studied by high performance liquid chromatography (HPLC). Using the dependence of log k vs pH, the hydrolysis of both the undissociated and dissociated XYL-molcules has been described by micro rate constants k₁ and k₂. Thermodynamic parameters (activation energy, enthalpy and entropy) of the composition reaction were calculated. This revised version was published online in June 2006 with corrections to the Cover Date.     

Kinetics and hazards of thermal decomposition of methyl ethyl ketone peroxide by DSC

Differential scanning calorimetry (DSC) was applied to analyze thermal decomposition of methyl ethyl ketone peroxide (MEKPO). Thermokinetic parameters and thermal stability were evaluated. MEKPO decomposes in at least three exothermic decomposition reactions and begins to decompose at 30–32 °C. The total heat of decomposition is 1.26 ± 0.03 kJ g⁻¹. Thermal decomposition of MEKPO can be described by a model of two independent reactions: the first is decomposition of a less stable isomer of MEKPO, followed by decomposition of the main isomer, after which an exothermic reaction of the reaction products with the solvent, dimethyl phthalate. The results can be applied for emergency relief system design and for emergency rescue strategies during an upset or accident.     

Thermal degradation of a composite solid propellant examined by DSC

The thermal decomposition of ammonium perchlorate (AP)/hydroxyl-terminated-polybutadiene (HTPB), the AP/HTPB solid propellant, was studied at different heating rates in dynamic nitrogen atmosphere. The exothermic reaction kinetics was studied by differential scanning calorimetry (DSC) in non-isothermal conditions. The Arrhenius parameters were estimated according to the Ozawa method. The calculated activation energy was 134.5 kJ mol^-1, the pre-exponential factor, A, was 2.04×1010 min^-1 and the reaction order for the global composite decomposition was estimated in 0.7 by the kinetic Shimadzu software based on the Ozawa method. The Kissinger method for obtaining the activation energy value was also used for comparison. These results are discussed here. This revised version was published online in August 2006 with corrections to the Cover Date.     

固相萃取-高效液相色谱-串联质谱法检测香辛料中罗丹明B

建立了香辛料中罗丹明B的固相萃取-高效液相色谱-串联质谱分析方法。样品经乙腈提取后离心,在提取液中加入10 mL 1%三氯乙酸溶液后,用Bond Elut Plexa PCX强阳离子固相萃取柱净化、富集,Pursuit C18色谱柱(100 mm×2.0 mm, 3 μm)分离,以0.1%甲酸水和甲醇为流动相梯度洗脱,电喷雾电离正离子模式下多反应监测(MRM)模式进行定性、定量检测。结果表明,在0.6～6 μg/L范围内的线性相关系数R2＞0.99;方法的定量限为1.2 μg/kg;添加量分别为1.197、2.992及5.985 μg/L时的加标回收率为80%～121%,相对标准偏差＜15%。同时对流动相的洗脱梯度、提取溶剂、固相萃取柱等条件进行了优化。该方法的专属性较强,基质效应较小,可用于固体香辛料产品中罗丹明B的定性、定量分析。