Spectrophotometric study of polythiazide—palladium(II) complex

A quantitative spectrophotometric method using Pd(II) chloride as analytical reagent for the determination of polythiazide in pharmaceutical preparations is described in this study. It has been found that polythiazide reacts with Pd(II) chloride in the pH range 3.6–5.8, forming a red, water-soluble (1:1) complex with maximum absorbance at 527 nm. At the optimum pH of 4.8 and an ionic strength μ = 0.1 M, the conditional stability constant of the complex is found to be log K′ = 4.77. The molar absorptivity at 527 nm is 3.2 × 10³ 1 mol⁻¹ cm⁻¹. Good agreement with Beer's law was found for polythiazide concentrations up to 2.2 mmol l⁻¹. The nominal percent recovery of polythiazide was 99.5% (n = 20). The simplicity, selectivity and sensitivity of the method described is suitable for rapid and accurate determinations of polythiazide in tablets.     

Sensitive spectrophotometric determination of amlodipine and felodipine using iron(III) and ferricyanide

A simple, accurate, sensitive and economical procedure for the estimation of amlodipine besylate and felodipine, both in pure form and in formulations has been developed. The method is based on the reduction of iron(III) by the studied drugs in acid medium and subsequent interaction of iron(II) with ferricyanide to form Prussian blue. The product exhibits absorption maximum at 760 nm in both cases. Beer's law is obeyed in the concentration ranges 5.0-15.0 and 1.5-5.0 microg/ml, for amlodipine and felodipine, respectively. The molar absorptivities are 1.76 x 10(4) and 4.24 x 10(4) l/mol cm. The corresponding Sandell sensitivities are 23.18 and 9.06 ng/cm(2). The limits of detection as well as quantification are reported. Seven replicate analyses of solutions containing three different concentrations of each drug were carried out and the percent error and the RSD values have been reported. The proposed method was applied to the determination of these drugs in pharmaceutical formulations and the results demonstrate that the method is equally accurate and precise as the official methods as found from the t- and F-values. The reliability of the method was established by recovery studies using standard-addition technique.     

Statistical optimization applied to the spectrophotometric study of a tolmetin—copper(II) complex

Tolmetin sodium has been investigated and determined from dosage forms as its Cu(II) complex and method optimized by statistical optimization. The assay was developed using two mathematical statistical models: factorial design and response-surface mapping. The decision to apply experimental design techniques to the development of the method was made after a series of screening experiments revealed that the complex formation and extraction are maximized as a function of supporting electrolyte concentration, concentration of Cu(II) acetate and pH of the reaction mixture. One set of two-level three variable factorial experiments was carried out in order to evaluate the main effect, as well as the interaction among factors. The final step was to optimize the values of variables using response surface design. The best set of conditions was selected for further investigation.     

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.     

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.     

Quantitative determination of some pharmaceutical piperazine derivatives through complexation with iron(III) chloride

A simple, accurate and sensitive spectrophotometric method has been developed for the determination of three pharmaceutical piperazine derivatives, namely ketoconazole (KC), trimetazidine hydrochloride (TMH) and piribedil (PD). This method is based on the formation of yellow orange complexes between iron(III) chloride and the investigated drugs. The optimum reaction conditions, spectral characteristics, conditional stability constants and composition of the water soluble complexes have been established. The method permits the determination of KC, TMH and PD over a concentration range 1-15, 1-12 and 1-12 microg ml(-1), respectively. Sandell sensitivity is found to be 0.016, 0.013 and 0.013 microg cm(-2) for KC, TMH and PD, respectively. The method was sensitive, simple, reproducible and accurate within +/-1.5%. The method is applicable to the assay of the three drugs under investigation in different dosage forms and the results are in good agreement with those obtained by the official methods (USP and JP).     

Investigation of the pindolol-Fe(III) complex and its use in the spectrophotometric determination of pindolol in bulk drug and tablets.

It was found that pindolol reacts with Fe(III) chloride producing a green water soluble complex (1:1, v/v) with maximum absorbance at 635 nm. By applying the methods of Sommer and Job [Sommer et al., Folia, tomus XI, Chemia 7, 25, 1970] the conditional stability constant of the complex at pH = 1.70 +/- 0.02 was found to be log K' = 4.95 and the molar absorptivity of the complex to be 206 l mol-1 cm-1. Beer's law was obeyed up to a concentration of 220 mumol l-1 of pindolol. The recoveries were 98-101% (n = 7) and the detection limit was 5 micrograms ml-1. The described method was sufficiently simple, selective and sensitive to be suitable for the rapid and accurate determination of pindolol in tablets.     

Use of palladium(II) chloride as colour-forming reagent in determination of pralidoxime chloride in water and tablets

Pralidoxime chloride (PAM-2Cl) has been determined spectrophotometrically in Britton—Robinson buffer solution at pH = 6.45; the method is based on measurement of the absorbance of the Pd(II)-pralidoxime complex at 327 nm. Studies of the composition of the complex by Job's continuous variation method, the molar ratio method and Bent—French's method yielded a Pd(II):pralidoxime ratio of 1:1. The conditional stability constant (K′) of the complex at the optimum pH of 6.45 and an ionic strength (μ) of 0.3 M was found to be 10^5.2. The molar absorptivity was 1.05 × 10⁴ 1 mol⁻¹ cm⁻¹. Beer's law was obeyed at concentrations up to 60 μM. The detection limit was 0.55 μg ml⁻¹. The relative standard deviation (N = 10) was 0.28–1.03%. The method was accurate and sensitive for the analysis of PAM-2Cl in water and tablets.     

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.     

Kinetic spectrophotometric methods for the determination of artificial sweetener (sucralose) in tablets

Two simple and sensitive kinetic spectrophotometric methods for the determination of sucralose are described. The first method is based upon a kinetic investigation of the oxidation reaction of the drug with alkaline potassium permanganate at room temperature for a fixed time of 30 min. The absorbance of the green coloured manganate ions produced was measured at 610 nm. The second method is based on the reaction of sucralose with cerium (IV) ammonium sulfate in the presence of perchloric acid with the subsequent measurement of the excess unreacted cerium (IV) ammonium sulfate at 320 nm at a fixed time of 30 min in a thermostated water bath at 60 ± 1 °C. This principle is adopted to develop a kinetic method for sucralose determination. The absorbance concentration plots in both methods were rectilinear over the range 4-16 and 10-30 μg ml(-1) , for the first and second methods, respectively. The different experimental parameters affecting the development and stability of the colours were carefully studied and optimized. The determination of sucralose by rate constant method, fixed concentration method, and fixed-time method was also feasible with calibration equations obtained but the latter method was found to be more applicable. The two methods have been applied successfully to commercial tablets.     

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.     

Selective spectrophotometric determination of phenolic β-lactam antibiotics

Two simple and selective spectrophotometric methods were developed for the quantitative determination of cefoperazone sodium, cefadroxil monohydrate, cefprozil anhydrous and amoxicillin trihydrate in pure forms as well as in their pharmaceutical formulations. The methods are based on the selective oxidation of these drugs with either Ce (IV) or Fe (III) in acid medium to give an intense yellow coloured product (λ_max=397 nm). The reaction conditions were studied and optimized. Beer's plots were obeyed in a general concentration range of 5–30 μg ml⁻¹ with correlation coefficients not less than 0.9979 for the four drugs with the two reagents. The methods are successfully applied to the analysis of pharmaceutical formulations containing amoxicillin, either alone or in combination with potassium clavulanate, flucloxacillin or dicloxacillin. They were also applied to the analysis of the other three studied drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 99.7 (±0.46) to 100.32 (±1.05) in the Ce (IV) method and 99.6 (±0.50) to 100.3 (±1.32) in the Fe (III) method. Interferences from other antibiotics and additives products were investigated.     

Cytotoxic activity of Gd(III)- and Dy(III)-complexes

The complexes of gadolinium(III) and dysprosium(III) were synthesized by reaction of the respective inorganic salts with 3,5-pyrazoledicarboxylic acid in amounts equal to metal to ligand molar ratio of 1 : 2. The structures of the final complexes were determined by means of spectral and elemental analyses. To help further the binding mode elucidation in the new Gd(III)- and Dy(III)-complexes of H(3)pdc, detailed vibrational analysis was performed on the basis of comparison of experimental vibrational spectra of the ligand and its Ln(III)-complexes using data theoretically predicted by us earlier, as well as data from the literature about related compounds. Significant differences in the IR and Raman spectra of the complexes were observed as compared to the spectra of the ligand. The ligand and the complexes were tested for their cytotoxic activities on the chronic myeloid leukemia-derived K-562, overexpressing the BCR-ABL fusion protein and the non-Hodgkin lymphoma-derived DOHH-2, characterized by a re-expression of the anti-apoptotic protein bcl-2 cell lines. The results obtained indicate that the tested compounds exerted a considerable cytotoxic activity upon the evaluated cell lines in a concentration-dependent manner, which enabled the construction of dose-response curves and the calculation of the corresponding IC(50) values. The inorganic salts exerted a very weak cytotoxic effect on these cells. This is in contrast to the lanthanide complexes, which exhibited potent cytotoxic activity, even more than the activity of cisplatin towards K-562 and DOHH-2 cell lines.     

Improved spectrophotometric determination of total iron and iron(III) with o-hydroxyhydroquinonephthalein and their characterization

Simultaneous and fractional determination of iron(II) and iron(III) was accomplished with o-hydroxyhydroquinonephthalein (QP) in the presence of poly (N-vinyl pyrrolidone). In the determination of total iron (iron(II)+iron(III)), Beer's law was obeyed in the range of 0.02-0.67 μg·ml(-1), with an effective molar absorptivity (at 570 nm) and a relative standard deviation of 1.30×10(5)·l·mol(-1)·cm(-1) and 0.77% (n = 8), respectively. This method was about 10-15 times and more than the methods using 1,10-phenanthroline and 2,2'-bipyridine. In addition, the iron-QP complex was characterized using spectrophotometry and the electron spin resonance. This method was successfully applied to assays of total iron and iron(III) in pharmaceutical preparations.     

Chromium(III) propionate complex supplementation improves carbohydrate metabolism in insulin-resistance rat model

The purpose of this study was to evaluate the antidiabetic potential and safety of the chromium(III) propionate complex (CrProp) in insulin resistance induced by a high-fructose diet in rats. The experiment was carried out on 32 nine-week old male Wistar rats divided into 4 groups of 8 rats each. Animals were fed at libitum: the control diet (AIN-93M), and high-fructose diets (HF) containing various levels of Cr(III) given as CrProp (1 mg Cr kg⁻¹ diet (HF) and supplemented with 10 mg Cr kg⁻¹ diet (HFCr10), or 50 mg Cr kg⁻¹ diet (HFCr50), equal to approx. 0.1, 1 and 5 mg kg⁻¹ body mass per day) for 8 weeks.     

Toxic effects of hexaammine cobalt(III) chloride on liver and kidney in mice: Implication of oxidative stress

Hexaammine cobalt (III) chloride is a trivalent complex cation of Co(III) and amine that has previously been shown to act as an inhibitor of insulin secretion, radiosensitizing agent, and an antiviral agent. We have recently reported the anticancer potential of the compound against diethylnitrosamine-induced carcinogenesis in mice. However, there is no report on the potential toxicity of the compound. The present study was conducted to evaluate the tissue distribution of the compound and its potential toxicity following acute administration of the compound through intraperitoneal route in Balb/c mice. Our results showed that cobalt accumulated maximally in kidney, followed by liver, spleen, blood, and lung in a decreasing order and in a dose-dependent manner. Evaluation of liver and kidney function tests revealed that the compound exerted a relatively higher toxicity in kidney, as compared to liver, as evidenced by the sharp enhancement in the serum levels of urea and creatinine in a dose-dependent manner. Examination of levels of lipid peroxidation and selected oxidative stress–related parameters in kidney, liver, and lung suggest that higher accumulation of cobalt in kidney may promote higher oxidative stress in the organ, as compared to liver and lung, which may eventually impair kidney function.     

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.