Iodine Method Research Articles

Spectrophotometric determination of clobetasol propionate, halobetasol propionate, quinagolide hydrochloride, through charge transfer complexation

Two spectrophotometric procedures are described for the determination of clobetasol propionate(I), halobetasol propionate(II) (corticosteroids) and quinagolide hydrochloride(III) (prolactin inhibitor). For corticosteroid drugs, the procedures are based on the formation of phenyl hydrazones of the corticosteroids which are subsequently subjected to charge transfer complexation reaction with either 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) as π-acceptor or with iodine as σ-acceptor. Prolactin inhibitor was reacted directly with the previous reagents. The molar ratios of the reactants were established and the experimental conditions were studied giving maximum absorption at 588 and 290 nm with DDQ and iodine methods, respectively for the three drugs. The concentration ranges were 20–150, 50–300, and 20–80 μg ml −1 in DDQ method for (I), (II), and (III), respectively and 13–20, 15–40, and 8–32 μg ml −1 in iodine method for (I), (II) and (III), respectively.

Selective radical reactions in multiphase systems: phase-transfer halogenations of alkanes.

The present paper shows that selective radical reactions can be initiated and carried out in multiphase systems. This concept is applied to the selective functionalization of unactivated aliphatic hydrocarbons, which may be linear, branched, and (poly)cyclic, strained as well as unstrained. The phase-transfer system avoids overfunctionalization of the products and simplifies the workup; the selectivities are excellent and the yields are good. This is the only method for direct preparative iodination of alkanes applicable to large scale as well. We demonstrate that the reaction systems are indeed phase-transfer catalyzed through a systematic study of variations of the reactants, solvents, catalysts, and by measuring as well as computing the H/D kinetic isotope effects for the rate-limiting C-H abstraction step by *CHal3 radicals which are held responsible for the observed radical reactions. In the case of *CBr3, this key intermediate could also be trapped under otherwise very similar reaction conditions. To stimulate further work, the tolerance of some functional groups was tested as well.

Use of charge-transfer complexation in the spectrophotometric analysis of certain cephalosporins

Three simple, rapid and sensitive spectrophotometric procedures were developed for the analysis of cephapirin sodium ( 1), cefazoline sodium ( 2), cephalexin monohydrate ( 3), cefadroxil monohydrate ( 4), cefotaxime sodium ( 5), cefoperazone sodium ( 6) and ceftazidime pentahydrate ( 7) in pure form as well as in their pharmaceutical formulations. The methods are based on the reaction of these drugs as n-electron donors with the σ-acceptor iodine, and the π-acceptors: 2,3-dichloro-5,6-dicyano- p-benzo-quinone (DDQ) and 7,7,8,8-tetracyanoquinodimethane (TCNQ). Depending on the solvent polarity, different coloured charge-transfer complexes and radicals were developed. Different variables and parameters affecting the reactions were studied and optimized. The obtained charge-transfer complexes were measured at 364 nm for iodine (in 1,2-dichloroethane), 460 nm for DDQ (in methanol) and 843 nm for TCNQ (in acetonitrile). Ultraviolet–visible, infrared and 1H-nuclear magnetic resonance techniques were used to study the formed complexes. Due to the rapid development of colours at ambient temperature, the obtained results were used on thin-layer chromatograms for the detection of the investigated drugs. Beer's plots were obeyed in a general concentration range of 6–50, 40–300 and 4–24 μg ml −1 with iodine, DDQ and TCNQ, respectively, with correlation coefficients not less than 0.9989. The proposed procedures could be applied successfully to the determination of the investigated drugs in vials, capsules, tablets and suspensions with good recovery; percent ranged from 96.47 (±1.14) to 98.72 (±1.02) in the iodine method, 96.35 (±1.62) to 98.51 (±1.30) in the DDQ method, and 95.98 (±0.78) to 98.40 (±0.87) in the TCNQ method. The association constants and standard free energy changes using Benesi–Hildebrand plots were studied. The binding of cephalosporins to proteins in relation to their molar absorptivities was studied.

A mild and efficient method for the regioselective iodination of pyrazoles

The iodination of N-H or N-benzylpyrazoles using elemental iodine in the presence of CAN as the in situ oxidant is a mild and efficient method to prepare 4-iodopyrazoles containing even electron-withdrawing substituents. The reaction is regioselective since the iodine atom preferred pyrazole instead of the benzyl group, and the 4-pyrazolic position instead of other possible positions in the heterocycle.

Changes in Cell Wall Polysaccharides of Kiwifruit and the Visco-elastic Properties Detected by a Laser Doppler Method.

Visco-elastic properties of kiwifruit were measured by a laser Doppler method over an eight day ripening period. After ethylene treatment, fruit flesh elasticity decreased exponentially. However, viscosity of the flesh increased from day 0 to 2 and then decreased. Fruit tissue was boiled in 80% ethanol to extract soluble sugars (EtOH fraction) ; the EtOH-insoluble residue was treated with α-amylase to solubilize starch. The amount of sucrose, glucose, fructose and inositol in the EtOH fraction on unit FW basis increased from day 0 to 3, while starch decreased during the ripening period. Cell wall material was fractionated into the hot water-soluble (WS), hot EDTA-soluble (pectin), alkaline soluble (hemicellulose) and residual (cellulose) fractions. The quantity of hydrolyzed sugars in the WS fraction decreased exponentially during ripening, whereas that in the pectin and hemicellulose fractions increased slightly on day 1 and then decreased rapidly. The amount of cellulose remained nearly constant during ripening. The iodine method revealed appreciable amounts of xyloglucan in the hemicellulose fraction. Gel permeation chromatography of polymers in the hemicellulose fraction revealed that xyloglucan had degraded rapidly by day 2. The molecular weights of both total sugar and uronic acid components of the pectin fraction increased from day 0 to 2, and then decreased. The amount of total cell wall polysaccharides and starch decreased by 80% during ripening, which indicates that a decrease in the molecular weight of xyloglucan correlates with a loss in fruit tissue elasticity, while the changes in the molecular weight of pectin corresponds with changes in viscosity. A substantial portion of the cell wall polysaccharides was hydrolyzed to soluble sugars in the early phase of ripening.

A DIRECT IODINATION METHOD WITH IODINE AND SILVER TRIFLATE FOR THE SYNTHESIS OF SPECT AND PET IMAGING AGENT PRECURSORS

A direct iodination method with iodine and silver triflate for the synthesis of SPECT and PET imaging agent precursors has been developed.

Iodination and Metal Halogen Exchange of Aromatic Compounds: An Improved Preparation of a Key Oxazolidinone Antibiotic Intermediate

A new method for the preparation of a key intermediate for oxazolidinone antibiotic analogues is discussed. We have found that iodine−magnesium exchange can be used to prepare a dianion if a fluorine is present ortho to the aryl anion and that exchange takes place on iodoanisoles. In addition, we report an improved method for iodination of aromatics using N-chlorosuccinimide/hydriodic acid and potassium iodide. By using these conditions, reactions are faster and higher-yielding than using either N-iodosuccinimide or iodine monochloride.

Spectrophotometric methods for the determination of lansoprazole and pantoprazole sodium sesquihydrate

Spectrophotometric procedures for determination of two irreversible proton pump inhibitors, lansoprazole (I) and pantoprazole sodium sesquihydrate (II) are presented. Two methods were based on charge transfer complexation reaction of these drugs, where they act as n-donors, with either π acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and with σ acceptor as iodine. A third method was also investigated depending on ternary complex formation with eosin and copper (II). The colored products were quantified spectrophotometrically using absorption bands at 457 nm for DDQ (method A) at 293 and 359 nm for iodine (method B) and at 549 nm using ternary complex formation (method C), for both drugs. The molar combining ratio and the optimum assay conditions were studied. These methods determined the lansoprazole in concentration ranges from 10 to 90, 1.48 to 6.65 and 3.69 to 16.61 μg ml −1 with mean percentage recovery 99.63% for DDQ, 99.71%, 99.18% for iodine and 99.76% for ternary complex and with relative standard deviation 0.11, 0.24, 0.13 and 0.36%, respectively. For pantoprazole, the concentration ranges were 10–60, 17.7–141.6 and 4.3–25.9 μg ml −1 with mean percentage recovery 99.51, 98.97, 99.84 and 99.46% and relative standard deviation 0.53, 1.21, 0.65, 0.81% for the three mentioned methods, respectively. Investigation of the formed complexes was made with respect to its composition, molar ratio of the reaction, association constant K C AD, molar absorptivity ε λ AD and free energy change Δ G for methods (A) and (B). The proposed methods have been applied successfully to the analysis of the cited drugs either in pure form or in pharmaceutical formulations, with good accuracy and precision, compared statistically with those given by the reported methods. They are recommended for quality control and routine analysis.

Chloramine-T in Radiolabeling Techniques: III. Radioiodination of Biomolecules Containing Thioether Groups

A previously reported method for iodination of the tyrosine moiety of oxidation-sensitive biomolecules was found to cause unacceptable damage to biomolecules containing thiols and thioether groups. This was due to the oxidation of the sulfur-containing residues by molecular iodine (I2). To selectively iodinate the tyrosine moiety with minimum oxidation to the sulfur functionality, studies of the kinetics of the reactions between I−3 and various amino acids and small peptides at various pH values in phosphate buffer were undertaken. Within the pH range studied (5.5–8.2), the results showed that the iodination reaction is strongly catalyzed by hydroxide ions, whereas the oxidation of the sulfur group was insensitive to pH. The results also showed that both reactions are strongly catalyzed by HPO−4 ion. In a complex molecule, such as methionine–enkephalin, oxidation of the methionine residue (undesirable reaction) proceeds in parallel with iodination of the tyrosine residue (desirable reaction). If such a molecule was iodinated in 0.01 M phosphate buffer at pH values above 7.5, the iodination reaction would proceed much more rapidly than the oxidation reaction, resulting in a high yield of iodinated substrate with little oxidative damage.

Iodination of TGF-beta, TGF-beta-receptor crosslinking, and immunoprecipitation of TGF-beta-receptor complexes.

Radioiodinated transforming growth factors ( TGF-βs) are critical reagents for functional studies on TGF-β ligand-receptor binding (, , , , ), TGF-β-binding protein interactions (, , , ), ligand uptake, degradation and clearance (,,), titering of TGF-β neutralizing antibodies (,), and for quantitation of TGF-βs by radioimmuno and radioreceptor assays (,). Several methods have been developed for the iodination of TGF-βs, namely chloramine T, lac-toperoxidase, and Bolton-Hunter (,,,). Although the latter method is gentler and believed to yield radiolabeled TGF-βs with greater biological activity than the first two, it is much more expensive, labor intensive and yields a poorly labeled product. Chloramine T is currently the most common method for iodination of TGF-βs, most likely because of its great efficiency of labeling. However, iodination with chloramine T can cause oxidative degradation of TGF-βs with excess treatment. For this reason, successful iodination of TGF-βs requires strict adherence to the amount of chloramine T used and the duration of treatment. Frolik et al. () have shown that three consecutive short treatments with low levels of chloramine T gives the best labeling with little oxidation of TGF-β. With the chloramine T method outlined later, all three isoforms of TGF-β can be iodinated with near-equal efficiency.

A quartz crystal microbalance method for the determination of iodine in foodstuffs

A quartz crystal microbalance (QCM) method to estimate the iodine content in foodstuffs is proposed. The method is based on sensitive response to mass change at electrodes of piezoelectric quartz crystal. After samples are decomposed, ionic iodine in the sample solution is changed to free iodine in acidic environment. Free iodine is then adsorbed at gold electrodes of QCM and iodine content in samples is estimated through decrease of QCM frequency. The method showed good reproducibility. Recovery of different concentrations of iodine added to food ranged from 93.2%-101.1%, with a mean and standard deviation of 96.9± 3.2 %. The detection limit of the method for iodine is 0.0005 mg/l in aqueous solution. No significant interferences are caused by anions such as Cl − , F − , NO 3 − , SO 4 2− , PO 4 3− and cations such as K + , Na + , Ca 2+ , Mg 2+ , Fe 3+ , Cu 2+ , Zn 2+ , Cd 2+ , Co 2+ , Ni 2+ , Bi 3+ . The only interference is found from bromine. The assay is also applicable for the determination of iodine in biological samples such as serum and urine.

Spectrophotometric determination of fluoxetine and sertraline using chloranil, 2, 3 dichloro-5, 6 dicyano benzoquinone and iodine

Spectrophotometric procedures are presented for the determination of two commonly used antidepressant drugs, fluoxetine (I) and sertraline hydrochloride (II). The methods are based mainly on charge transfer complexation reaction of these drugs with either π acceptors chloranil and 2, 3 dichloro-5, 6-dicyanoquinone (DDQ) or σ acceptor iodine. The colored products are quantified spectrophotometrically at 550, 450 and 263 nm for fluoxetine and at 450, 455 and 290 nm for sertraline in chloranil, DDQ and iodine methods, respectively. The molar combining ratio and the optimum assay conditions were studied. The methods determine the cited drugs in concentration ranges of 80–640, 16–112 and 7.5–60 μg/ml with mean percentage recoveries of 99.83, 99.76 and 100.00% and R.S.D. of 1.24, 0.95 and 1.13% in fluoxetine and ranges of 16–160, 15–105 and 6–48 μg/ml with mean percentage recoveries of 100.39, 99.78 and 99.69% and R.S.D. of 1.02, 0.81 and 0.57% in sertraline for chloranil, DDQ and iodine methods, respectively. A more detailed investigation of the complex formed was made with respect to its composition, association constant K c AD , molar absorptivity ξ A AD and free energy change Δ G. The proposed methods were applied successfully to the determination of the cited drugs either in pure or dosage forms with good accuracy and precision. The results were compared statistically with those given by the reported methods.

Interaction of thrombopoietin with the platelet c-mpl receptor in plasma: binding, internalization, stability and pharmacokinetics.

Thrombopoietin (TPO) is the primary regulator of platelet production and acts through binding its receptor, c-mpl, found on megakaryocyte progenitor cells, megakaryocytes and platelets. Circulating levels of TPO are regulated primarily by the clearance of TPO after it binds to c-mpl receptors on circulating platelets. In this study the interaction of TPO with the platelet c-mpl receptor has been analysed under physiological conditions using radiochemical and pharmacokinetic approaches. 125I-rHuTPO was prepared using a novel method of gentle iodination that preserved its biological activity and used to demonstrate that platelets, but not endothelial cells, have a single class of binding sites (56 +/- 17 binding sites/platelet) with high affinity (Kd = 163 +/- 31 pM). Cross-linking experiments confirmed that TPO, but not erythropoietin (EPO), specifically associated with the 95 kD platelet c-mpl receptor. Upon addition of TPO to platelets, 80% of the TPO binding sites were internalized within an hour and were not recycled. TPO that was not bound by platelets was stable for up to 6 d in both platelet-poor and platelet-rich plasma. Using unlabelled recombinant human TPO (rHuTPO), standard pharmacokinetic analysis demonstrated that platelets have an average TPO clearance of 1.24 +/- 0.38 ml/h/109 platelets and that TPO clearance was reduced by low temperature but not by a number of drugs or metabolic inhibitors. The maximal amount of TPO removed by platelets in vitro was identical to that predicted by the total number of TPO binding sites. These results provide a biochemical and pharmacokinetic basis for the clinical use of TPO and for understanding possible disorders of platelet production.

Colorimetric and Fluorimetric Methods for the Determination of Some Antihistaminics Using Acid Dyes and Charge Transfer Techniques

The acid dyes eosin B and tropeolin oo were used for the determination of terfinadine, astemizole and acrivastine in the presence of Mcllvain buffer of a suitable pH. The formed ion-pairs were extracted with chloroform and the absorbances were measured at 530–535 nm and 410 nm in the case of eosin B and tropeolin oo, respectively. In addition terfinadine, astemizole and acrivastine were determined fluorimetrically using eosin B. The fluorescence intensity was measured at 480 nm excitation and 555 nm emission. Conformity with Beer's law was evident over a concentration range of 2–20 μg/ml in the colorimetric methods and of 0.16 – 0.96 μg/ml in the fluorimetric methods. The charge transfer technique was also applied for the determination of astemizole and acrivastine using iodine and 2,3 dichloro, 5, 6 – dicyano – p-benzoquinone (DDQ). Absorbances were measured at 286 nm and 292 nm, respectively, in the iodine method, and at 461 nm in the DDQ method. Conformity with Beer's law was evident over concentration range of 1 – 12 μg/ml and 20 – 200 μg/ml in iodine and DDQ methods respectively. The precision of the proposed methods was tested by applying them for the determination of pure samples of terfinadine, astemizole and acrivastine. The mean percentage recovery of terfinadine, astemizole and acrivastine lies in the range 99.49-100.72% in eosin B method, 99.79-100.16% in tropeolin oo method, 100.01-101.00% in the fluorimetric method. In the charge transfer methods the mean percentage recovery of astemizole and acrivastine lies in the range 99.61-100.40% and 100.02-100.30% in iodine and DDQ methods respectively. The proposed methods were successfully applied for the determination of the drugs in their pharmaceutical dosage forms and their validities were ascertained by applying the standard addition technique.

Selective and Efficient Iodination of the p-Positions of Calix[4]arene Derivatives

Selective and very convenient methods of iodination of calix[4]arenes using ICl or NIS have been demonstrated, preparing mono(p-iodo) and 1,3-di(p-iodo) derivatives of calix[4]arenecrown-4 and -5, as well as mono(p-iodo) derivative of tris(O-propyl)calix[4]arene in good yields.

A mild and effective iodination method using iodine in the presence of bis-(trifluoroacetoxy)iodobenzene

Herein is described a mild and effective iodination method using bis-(trifluoroacetoxy)iodobenzene-iodine as reagent to be applied to electron deficient heterocyclic systems (protected indoles, coumarin…) Moreover, sensitive protecting groups such as acetyl and tert-butyldimethylsilyl were found to be stable under the new iodination reaction conditions.

Determination of total iodine in nutritional and biological samples by ICP-MS following their combustion within an oxygen stream.

A mineralization and determination method for total iodine in nutritional and biological samples is described. Combustion of the sample in an oxygen stream is followed by collection of the combustion products in a 5% water-soluble tertiary amine solution. Iodine is determined by inductively coupled plasma mass spectrometry. The accuracy and precision of the quantitative iodine analysis using standard addition is better than +/- 10%. A semi-quantitative analysis of four standard reference materials is evaluated. Owing to the presence of low-level iodine contaminant in the blank solution, the determination limit of the method is +/- 10 micrograms kg-1. Good agreement with certified iodine values is obtained for six reference materials. The use of the tertiary amine matrix solution permits the simultaneous determination of iodine and other trace metals of biological and toxicological importance, including Mn, Co, Ni, Cu, Zn, Rb, Cd, and Pb.

The Direct Iodination of Arenes with Chromium(VI) Oxide as the Oxidant

Abstract An easy and cheap laboratory method is presented for the direct mono- and diiodination of a number of activated and deactivated arenes. The main iodination reactions occurred at the temperatures not exceeding 65 °C for 0.5—12 h in the anhydrous, strongly acidic liquid system, I2/AcOH/Ac2O/H2SO4, in the presence of prior dissolved CrO3 used as the oxidant. The yields of the pure iodinated products varied from 31% (for 3,5-diiodobenzoic acid) up to 90% (for 4-iodoanisole). So far, benzonitrile and some oxidizable aromatics, e.g. naphthalene, fluorene, xanthene, and thiophene, have been found to be unsuitable for the effective iodination. Nevertheless, this novel, simple method of direct iodination is worthy to be extended to other appropriate aromatics.

Validation of a simple, manual urinary iodine method for estimating the prevalence of iodine-deficiency disorders, and interlaboratory comparison with other methods

The measurement of urinary iodine in population-based surveys provides a biological indicator of the severity of iodine-deficiency disorders. We describe the steps performed to validate a simple, inexpensive, manual urinary iodine acid digestion method, and compare the results using this method with those of other urinary iodine methods. Initially, basic performance characteristics were evaluated: the average recovery of added iodine was 100.4 +/- 8.7% (mean +/- SD), within-assay precision (CV) over the assay range 0-0.95 mumol/L (0-12 micrograms/dL) was < 6%, between-assay precision over the same range was < 12%, and assay sensitivity was 0.05 mumol/L (0.6 microgram/dL). There were no apparent effects on the method by thiocyanate, a known interfering substance. In a comparison with five other methods performed in four different laboratories, samples were collected to test the method performance over a wide range of urinary iodine values (0.04-3.7 mumol/L, or 0.5-47 micrograms/dL). There was a high correlation between all methods and the interpretation of the results was consistent. We conclude that the simple, manual acid digestion method is suitable for urinary iodine analysis.

Use of iodinated bread for preventing endemic goiter in regions with moderate and slight iodine deficit

Iodination of foodstuffs is one basic trend in prevention of iodine deficit and diseases caused by it. The production of iodine salt is rather expensive, and hence, another highly prevalent foodstuff was chosen as "iodine carrier": bread. Bread is traditional food in Russia and its consumption is stable throughout the year. Bread baking is centralized in the majority of regions of our country. It is manufactured at rather large bakeries and delivered even to the most faraway regions. In order to solve the practical problems of baking iodinated bread, a pilot experiment was carried out in 1993-1995 in the Pavlovsky Posad district near Moscow (a region with moderate and slight iodine deficiency). The experiment was sponsored by the UNICEF (UN Childhood Foundation) and included development of the formula of bread iodination and assessment of this method of iodine prophylaxis. According to the proposed formula, 60 mg of potassium iodide is to be added per 100 g of flour; such a dose covers the daily requirement of an organism in iodine, provided 500 g of bread is consumed daily. The efficacy of iodinated bread was assessed from the time course of renal excretion of iodine and incidence of thyroid enlargement in 162 schoolchildren aged 7 to 14 at a boarding school in the town of Pavlovsky Posad, who were given 300 g of bread daily, and in 178 schoolchildren aged 9 to 11 living in the rural regions, eating about 100 g daily. After 3 months the median level of urinary iodine increased from 4.8 to 12.6 pg% in town and from 3.0 to 6.2 pg% in the country. After 9 months the levels of urinary excretion of iodine were the same, moreover, the incidence of thyroid enlargement decreased in both groups. Hence, the tasks of pilot experiment were fulfilled: a method for bread iodination has been developed and introduced at bakeries and its efficacy in normalization of iodine supply validated.