An application of Ag(III) complex chemiluminescence system for the determination of enoxacin in capsule and biological fluid

Ag(III) complex chemiluminescence (CL) system was applied for the determination of enoxacin (ENX). The CL conditions of [Ag(HIO(6))(2)](5-)-H(2)SO(4)-ENX systems without any luminescence reagent were investigated and optimized. Under the optimized conditions, the CL intensity was proportional to the concentration of ENX in the range from 6.6 × 10(-5) to 3.3 × 10(-3) g/L. The limit of detection (s/n = 3) was 2.0 × 10(-5) g/L. The recovery of ENX from the spiked pharmaceutical preparations was in the range of 82.9-108% with a relative standard deviation of 1.9-3.0%. For spiked serum and urine samples the recovery of ENX was in the range of 83.7-110% with a relative standard deviation of 1.1-2.8%. The proposed method was applied successfully to the determination of the drug in capsule, serum and urine samples.     

A sensitive flow injection chemiluminescence method for the determination of progesterone

A sensitive flow injection (FI) chemiluminescence (CL) method was developed for the determination of trace amounts of progesterone. This method was based on the luminescent properties of the tris(1,10‐phenanthroline) ruthenium(II) ‐ potassium permanganate (KMnO₄) ‐ progesterone in acidic medium sensitized by Na₂SO₃. With the peak height as a quantitative parameter applying optimum conditions, the relative CL intensity was linear with progesterone concentration in the range of 1.0 × 10^?10 ～ 6.0 × 10^?9 g·ml^?1 and 6.0 × 10^?9 ～ 4.0 × 10^?8 g·ml^?1 with a detection limit of 7.1 × 10^?11 g·ml^?1. The relative standard deviation (RSD) was 2.79% for 1.0 × 10^?8 g·ml^?1 progesterone (n = 11). The proposed method held low detection limit and was successfully applied to determination of progesterone in pharmaceutical preparations. The possible CL reaction mechanism was also discussed. Copyright © 2011 John Wiley & Sons, Ltd.     

A novel flow‐injection chemiluminescence method for determination of andrographolide in andrographis tablets

A novel method for determination of andrographolide using flow‐injection chemiluminescence (FI‐CL) analysis is described in this paper. The chemiluminescence intensity of the solution was enhanced proportionally while the concentration of andrographolide increased. Under the selected experimental conditions, the calibration curve of andrographolide was linear within the range of 0.2 to 35.0 µg mL^?1 with a linear equation of ΔI = 23.391x (µg mL^?1) + 34.191, R² = 0.9965. The detection limit (3σ) was 7.42 × 10^?2 µg mL^?1. At the case of continuous determination of andrographolide, the relative standard deviation (RSD, n = 11) was less than 1.82%. The method has been successfully applied to the determination of andrographis tablets with satisfactory results. Copyright © 2012 John Wiley & Sons, Ltd.     

Spectrophotometric determination of alendronate in pharmaceutical formulations via complex formation with Fe(III) ions

The formation of the complex between alendronate, non-chromophoric bisphosphonate drug important for the treatment of a variety of bone diseases, and iron(III) chloride in perchloric acid solution was studied. The stoichiometric ratio of alendronate to Fe(III) ions in the chromophoric complex was determined to be 1:1. The conditional stability constant was log K′_ave=4.50 (SD=0.15), indicating that the Fe(III)–alendronate complex is a complex of medium stability. The optimum conditions for this reaction were ascertained and a spectrophotometric method was developed for the determination of alendronate in the concentration range 8.1–162.5 μg ml⁻¹, the detection limit being 2 μg ml⁻¹. The method was validated for the direct determination of alendronate in tablet dosage formulations.     

Dysprosium‐sensitized chemiluminescence system for the determination of enoxacin in pharmaceutical preparations and biological fluids with flow‐injection sampling

A novel trivalence dysprosium(Dy³⁺)‐sensitized chemiluminescence method was developed for the first time for the determination of enoxacin (ENX) using flow‐injection sampling based on the chemiluminescence (CL) associated with the reaction of the Dy³⁺‐cerium(Ce(IV))‐S₂O₃^2?‐ENX system and the Dy³⁺‐MnO₄^? S₂O₃^2?‐ENX system. The analytical conditions for CL emission were investigated and optimized. The relationship between the CL intensity of ENX and its concentration has good linearity, with a correlation coefficient of 0.9984–0.9994. The limit of detection (LOD, 3σ) was 0.20 ng/mL for the Dy³⁺‐ENX‐S₂O₃^2?‐Ce(IV)‐H₂SO₄ system and 0.22 ng/mL for the Dy³⁺‐ENX‐S₂O₃^2?‐MnO₄^?‐HNO₃ system. The relative standard deviation (RSD, n = 11) was 1.8% for 11 determinations of 60 ng/mL ENX. The proposed method was applied to the analysis of ENX in injections, serum and urine samples with a recovery of 98%–105%. A possible mechanism for this sensitized CL reaction is discussed by comparing the CL spectra with the fluorescence emission spectra. The proposed method represents a wide linear range, high sensitivity and accuracy, and can be used for the routine determination of ENX in pharmaceutical preparations and biological fluids. Copyright © 2009 John Wiley & Sons, Ltd.     

Validation of a spectrophotometric method for the determination of iron (III) impurities in dosage forms

A spectrophotometric method (λ=535 nm) for the iron (III) impurities determination in iron protein–succinylate complex syrup using thioglycolic acid in basic ambient was proposed and validated. Assay samples were treated with 0.1 N hydrochloric acid and centrifuged to remove the interfering active drug. Linear response (r=0.9999) was observed over the range of 0.005–0.2% of the iron (III) with respect to the complex nominal concentration. The accuracy could be considered very satisfactory (recovery=97–99%). The intra-day precision (RSD) of impurity amongst six independent sample preparations, was 1.4%, and there was no significant difference between intra- and inter-day studies. Intermediate precision indicated that the assay possessed high degrees of ruggedness. The limit of quantitation was 0.005% of impurity with respect to the active drug. The results obtained for iron (III) were compared statistically with those obtained with the standard addition method by means of the Student's t-test and the variance ratio F-test; no significative difference was found.     

Investigation of penbutolol—iron(III) complex and its spectrophotometric determination in tablets

It has been established that penbutolol reacts with iron(III) chloride in the presence of ammonium thiocyanate to form a pink complex (2:1) that is soluble in chloroform with a maximum absorbance at 478 nm. By application of the methods of Sommer and Job involving non-equimolar solutions, the conditional stability constant (log k′) of the complex at the optimum pH of 1.5±0.02 and an ionic strength of (μ) 0.14 M, was found to be 5.769. The molar absorptivity at 478 nm was 136 l mol⁻¹ cm⁻¹ at pH 1.5±0.02. The validity of Beer's law has been tested in the concentration range 3–18 × 10⁻⁴ M; the relative standard deviation (n = 8) was 1.52–3.21%. The proposed method was found to be suitable for the accurate, simple and rapid analysis of penbutolol in the bulk drug and in tablets.     

The effects of tricentric chromium(III) propionate complex supplementation on pregnancy outcome and maternal and foetal mineral status in rat

Chromium(III) is an essential element for carbohydrate and lipid metabolism, and various chemical forms of this element are widely used as dietary supplements. Of particular interest is [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]⁺ cation (CrProp), that has been proposed as an alternative source of Cr. However, its safety has not been studied completely. In this study we investigated the effects of CrProp supplementation on pregnancy outcome and maternal and foetal mineral status in the rat. Female Wistar rats (n = 20, 14 weeks old) were mated with males and, after successful conception were fed either AIN-93G diet supplemented with CrProp (100 mg Cr/kg diet, equals to 7.2 mg Cr/kg body mass/day) or non-supplemented diet (0.27 mg Cr/kg diet, equals to 0.02 mg Cr/kg body mass/day) for 21 days. Dams were sacrificed on 21 day of gestation, and their foetuses were examined for adverse effects. Maternal and foetal organs were analysed for minerals contents (Fe, Cu, Zn, Cr) using the AAS-method. Supplemental Cr given did not affect pregnancy outcome, litter size, body and inner organ masses, maternal blood biochemical indices. No abnormalities in gross organ morphology of foetuses were detected. Supplemental CrProp increased maternal liver and kidney Cr levels by 177% and 455%, decreased liver Cu and Zn concentrations by 9% and 12%, increased foetal liver Zn by 181%, and decreased kidney Cu level by 34%.     

Evaluation of the acute oral toxicity class of tricentric chromium(III) propionate complex in rat

Chromium(III) is an essential element for carbohydrate and lipid metabolism, and various chemical forms of this element are widely used in dietary supplements. Of particular interest is [Cr₃O(O₂CCH₂CH₃)₆(H₂O)₃]⁺ cation (CrProp), that has been proposed as an alternative source of Cr. However, its safety has not been studied completely. In this study, we evaluated the acute toxicity class of CrProp in Wistar rats applying the OECD 423 procedure. Male and female Wistar rats (n = 12, 6 ♀ and 6 ♂) were given by gavage either a single dose of CrProp 2000 mg kg⁻¹ body mass or equivalent volumes of distilled water, and fed Labofeed B diet, and observed carefully for 14 days, than sacrificed to collect samples for biochemical and histologic examination. No death cases were detected, no major abnormalities in animal behaviour, body mass gains, gross organ histology, and blood morphology, and biochemistry were observed, except some changes of liver mass and the activity of ALT in female rats. The results demonstrate that LD₅₀ of CrProp is greater than 2000 mg kg⁻¹ when administrated orally to rat, thus this compound appears to be belong the fifth category in the GHS system or the fourth class (“unclassified”) in the EU classification system.     

Evaluation of anti-diabetic potential of chromium(III) propionate complex in high-fat diet fed and STZ injected rats

The aim of this study was to examine the anti-diabetic potential of the chromium(III) propionate complex (CrProp) in a diabetic rat model. Male Wistar rats (n = 28, 8-week old) were divided into 4 groups (with 7 rats each) and fed at libitum: the control diet (AIN-93M), and high-fat diets with or without supplementary CrProp (10 and 50 mg Cr kg⁻¹ diet; 1 and 5 mg kg⁻¹ body mass per day) for 5 weeks, and subsequently injected with STZ to induce diabetes. Rats were further fed the same diets for another week until the end of the experiment. Blood indices and the contents of minerals (Fe, Zn, Cu and Cr) in rat tissues were determined by atomic absorption spectrometry. Supplementary CrProp did not affect blood glucose level, but significantly improved insulin sensitivity (HOMA-IR index) and reduced serum levels of triacylglycerols, total and LDL cholesterols. Both supplementary dosages of CrProp (10 and 50 mg Cr kg⁻¹ diet) normalized the increased liver Fe content, reduced hepatic and renal Cu levels and elevated renal Cr contents in diabetic rats. In conclusion, CrProp has a significant anti-diabetic (insulin-sensitizing and hypolipidemic) potential; thus it might be a candidate for a therapeutic agent in diabetes.     

铬(Ⅲ)配合物治疗高脂蛋白血症95例

本文报道用铬(Ⅲ)配合物治疗各型高脂蛋白血症95例的临床疗效。采用自身单盲前后对照观察,先服安慰剂1.5mo,继服本药5mg bid 1.5mo。血清总胆固醇增高者42例,治疗后平均下降0.7mmol/1,总有效率65％。甘油三酯增高者89例,平均下降1.4 mmol/1,总有效率74％。治疗后各项血脂水平改变与服安慰剂后相比有非常显著性差异(P<0.01)。治前同时血糖增高者,亦有明显下降,平均下降0.74 mmol/1。血液流变学指标亦有不同程度的改善。治疗中未发现有毒副反应。本药为一种治疗脂质及糖代谢紊乱的有效药物,值得进一步研究。     

Genotoxicity assessment of chromium(III) propionate complex in the rat model using the comet assay

The aim of the study was to assess genotoxicity of a chromium(III) propionate complex in rat’s peripheral blood lymphocytes by the comet assay. The study was carried out on 18 12-weeks old female Wistar rats that were divided into three equal groups (six animals each): control (0), control-Cr(VI) and Cr(III)-tested rat fed ad libitum a basal diet and the diet supplemented either with 10 mg Cr(VI)/kg diet (given as K₂Cr₂O₇, equivalent of 1 mg/kg body mass/day) or 1000 mg Cr(III)/kg diet (given as [Cr₃O(O₂CCH₂CH₃)6(H₂O)₃]NO₃), equivalent of 100 mg Cr/kg body mass/day) for 4 weeks. High doses of supplementary Cr(III) were found to not affect body mass gain, feeding efficiency ratio and internal organ masses. Treatment of rats with the Cr(III) propionate complex, in contrast to Cr(VI), did not affect significantly the comet assay results in lymphocytes, which suggests that the compound does not exert genotoxic effects in rats.     

Self-assembly of Ophiopogonis polysaccharide-iron (III) complex in aqueous solution and solid state

Ophiopogonis polysaccharide-iron (III) (OPI) was prepared and characterized in the present study. The optimum condition for preparing OPI was as follows: OP and trisodium citrate were mixed at a weight ratio of 4:1 and reacted in a water bath at 70 °C for 3 h within the pH range of 8.0–8.5. Aggregation morphology or structure of OPI in aqueous solution and solid state was studied by scanning electron microscopy, transmission electron microscopy and small-angle X-ray diffraction. In aqueous solution, OPI could self-assemble into micron vesicles with flower-shaped morphology. Results of X-ray diffraction showed OPI with layered structure. A core-shell model was proposed for OPI.     

Application of novel Ni(II) complex and ZrO2 nanoparticle as mediators for electrocatalytic determination of N-acetylcysteine in drug samples

The electrooxidation of N-acetylcysteine (N-AC) was studied by a novel Ni(II) complex modified ZrO₂ nanoparticle carbon paste electrode [Ni(II)/ZrO₂/NPs/CPE] using voltammetric methods. The results showed that Ni(II)/ZrO₂/NPs/CPE had high electrocatalytic activity for the electrooxidation of N-AC in aqueous buffer solution (pH = 7.0). The electrocatalytic oxidation peak currents increase linearly with N-AC concentrations over the concentration ranges of 0.05–600μM using square wave voltammetric methods. The detection limit for N-AC was equal to 0.009μM. The catalytic reaction rate constant, k_h, was calculated (7.01 × 10² M⁻¹ s⁻¹) using the chronoamperometry method. Finally, Ni(II)/ZrO₂/NPs/CPE was also examined as an ultrasensitive electrochemical sensor for the determination of N-AC in real samples such as tablet and urine.     

Electrogenerated chemiluminescence sensor for metoclopramide determination based on Ru(bpy)3 2+-doped silica nanoparticles dispersed in Nafion on glassy carbon electrode

A novel method for the determination of metoclopramide (MCP) using electrogenerated chemiluminescence (ECL) is presented. A tris(2,2'-bipyridyl)dichlororuthenium(II) (Ru(bpy)3(2+))-doped silica (RuDS) nanoparticle/perfluoinated ion-exchange resin (Nafion) with nanocomposite membrane modified glassy carbon electrode (GCE) is used. The Ru(bpy)3(2+) encapsulation interior of the silica nanoparticle maintains its electrochemical activities and also reduces Ru(bpy)3(2+) leaching from the silica matrix when immersed in water due to the electrostatic interaction. The analytical performance of this ECL sensor for MCP is shown in detail. Under optimal experimental conditions, it has good linearity in the concentration range from 2 x 10(-8)mol/L to 1 x 10(-5)mol/L (R=0.9989) with a detection limit of 7 x 10(-9)mol/L. The relative standard deviation (n=11) is 3.2% for detecting 1.2 x 10(-6)mol/L MCP. The recoveries are in the range of 97.0-104.4% for sample measurements by standard-addition method. This method has been applied successfully to determine MCP in pharmaceutical preparations and in human urine. Statistical analysis (Student's t-test and variance ratio F-test) of the obtained results show no significant difference between this proposed method and the reference method.     

A novel GC-MS method for rapid determination of headspace oxygen in vials of pharmaceutical formulations

A novel GC-MS method which requires small injection volumes was developed for fast and selective determination of headspace oxygen in pharmaceutical packages. This method does not require a specific GC column for separation of oxygen from other permanent gases such as nitrogen; instead it offers the advantage of using co-eluting nitrogen as the internal standard for quantifying oxygen in the headspace under electron ionization (EI, 70eV) conditions. The relative ionization efficiency of oxygen to nitrogen, termed as ionization efficiency correction factor (IECF), can be measured using a control sample with known composition of oxygen and nitrogen such as the standard dry air used in this study. To avoid contamination, it is necessary to flush the syringe with pure helium. The measurements by the method are independent of the variations of sampling volumes. The determined headspace oxygen contents (R.S.D.<1%) in the containers of an investigational intravenous formulation using this method are consistent with the results obtained by an oxygen instrument at the manufacturing facility. The performance of the analytical approach was evaluated in the study of the container closure integrity at various storage conditions including upright and inverted orientations. The results suggest that there is no obvious oxygen penetration over 12 months. This method provides a convenient tool for measuring the levels of HS oxygen in vials of pharmaceutical formulations.     

Chromium(III) complexes of D-glucosaminic acid and their effect on decreasing blood sugar in vivo

Two chromium(III) complexes of glucosaminic acid were synthesized by neutralization and exchange reaction. The formation of 1 : 1 and 2 : 3 (Cr : glucosaminate) complexes was confirmed by elemental analyses and spectroscopic studies. The effect of the complexes on decreasing blood sugar was investigated on type-2 diabetes model rats induced by tetraoxypyrimidine. The results indicated that the effect on decreasing blood sugar was comparable to that of picolinate chromium complex (Cr(pic)(3)) currently used world wide.     

Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III) prodrug of a chloromethylbenzindoline DNA minor groove alkylator

Metabolic reduction can be used to activate prodrugs in hypoxic regions of tumours, but reduction by ionising radiation is also theoretically attractive. Previously, we showed that a cobalt(III) complex containing 8-hydroxyquinoline (8-HQ) and cyclen ligands releases 8-HQ efficiently on irradiation in hypoxic solutions [Ahn G-O, Ware DC, Denny WA, Wilson WR. Optimization of the auxiliary ligand shell of cobalt(III)(8-hydroxyquinoline) complexes as model hypoxia-selective radiation-activated prodrugs. Radiat Res 2004;162:315-25]. Here we investigate an analogous Co(III) complex containing the potent DNA minor groove alkylator azachloromethylbenzindoline (azaCBI, 1) to determine whether it releases 1 on radiolytic and/or enzymatic reduction under hypoxia. Monitoring by HPLC, the azaCBI ligand in the Co(III)(cyclen)(azaCBI) complex (2) slowly hydrolysed in aqueous solution, in contrast to the free ligand 1 which readily converted to its reactive cyclopropyl form. Irradiation of 2 (30-50 microM) in hypoxic solutions released 1 with yields of 0.57 micromol/J in formate buffer and 0.13 micromol/J in human plasma. Using bioassay methods, cytotoxic activation by irradiation of 2 at 1 microM in hypoxic plasma was readily detectable at clinically relevant doses (> or = 1 Gy), with a estimated yield of 1 of 0.075 micromol/J. Release of 1 from 2 was also observed in hypoxic HT29 cultures without radiation, with subsequent conversion of 1 to its O-glucuronide. Surprisingly, overexpression of human cytochrome P450 reductase in A549 cells did not increase the rate of metabolic reduction of 2, suggesting that other reductases and/or non-enzymatic reductants are responsible. Thus the cobalt(III) complex 2 is a promising prodrug capable of being activated to release a very potent cytotoxin when reduced by either ionising radiation or cells under hypoxic conditions.     

Simultaneous determination of Fe(II) and Fe(III) in pharmaceutical formulations with chromogenic mixed reagent by using principal component artificial neural network and multivariate calibration

The use of chemometric approaches for the simultaneous determination of Fe(II) and Fe(III) ions has been explored by means of a two component reagent. Mixed reagents of 1,10-phenanthroline and thiocyanate were used as a selective chromogenic system for speciation of Fe(II) and Fe(III). Although the complexes of Fe(II) and Fe(III) with mixed reagent show a spectral overlap, they have been simultaneously determined with chemometric approaches, such as principal component artificial neural network (PC-ANN), principal component regression (PCR) and partial least squares (PLS). A set of synthetic mixtures of Fe(II) and Fe(III) was evaluated and the results obtained by the applications of these chemometric approaches were discussed and compared. It was found that the PC-ANN and PLS methods afforded better precision relatively than its of PCR. PC-ANN and PLS methods were also applied satisfactorily in determination of Fe(II) and Fe(III) in pharmaceutical samples.     

Spectrophotometric determination of gliclazide in pharmaceuticals and biological fluids through ternary complex formation with eosin and palladium (II)

A simple and sensitive spectrophotometric method has been developed for the determination of gliclazide (GLZ) in pharmaceutical formulations and biological fluids. The proposed method is based upon the formation of a ternary complex between palladium (II), eosin and GLZ in the presence of methyl cellulose as a surfactant and acetate buffer of pH 4.5. The ternary complex showed an absorption maximum at 550 nm. The solution of ternary complex obeyed Beer's law over the concentration range of 0.5-4 microg ml(-1) with minimum detectability (S/N = 2) of 0.05 microg ml(-1) (1.545 x 10(-7) M). The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. The proposed method was successfully applied to the analysis of commercial tablets. The results obtained were in good agreement with those obtained using the official or reference spectrophotometric method. The proposed method was further applied to spiked human urine and plasma, the percentage recoveries were 97.84 +/- 0.72 and 97.43 +/- 0.83, respectively, (n = 4). A proposal of the reaction pathway was presented.