New chemistry supporting portable solutions for end-stage renal disease dialysis treatment.

A new polymeric adsorbent to improve portable dialysis treatment by simplifying urea removal at the dialysate regeneration step is proposed. An adsorbent to remove urea was synthesized by molecular imprinting technology that can potentially overcome drawbacks existing in urease enzyme-based dialysate regeneration technology. Molecularly imprinted polymer (MIP) for urea generates cavities both in shape and in size targeted for urea. Using the synthesized MIP, we have shown removal of urea present in the dialysate buffer. Various experimental conditions such as choice of monomers, porogen, and template to monomer ratios were optimized to achieve highest binding capacity on a column flow through system monitored using high-performance liquid chromatography (HPLC). Taking advantage of the basicity of urea molecule, monomers having Brønsted acidic groups such as acrylic acid, methacrylic acid and itaconic acid were screened. The MIP synthesized using urea:acrylic acid:EGDMA (1:4:12) in acetonitrile:ethylene dichloride (1:1) as porogen gave highest binding capacity of 24.5 g/kg of urea in the dialysate buffer matrix.

In situ spectroscopic studies on vapor phase catalytic decomposition of dimethyl oxalate.

Dimethyl Oxalate (DMO) has recently gained prominence as a valuable intermediate for the production of compounds of commercial importance. The stability of DMO is poor and hence this can result in the decomposition of DMO under reaction conditions. The mechanism of DMO decomposition is however not reported and more so on catalytic surfaces. Insights into the mechanism of decomposition would help in designing catalysts for its effective molecular transformation. It is well known that DMO is sensitive to moisture, which can also be a factor contributing to its decomposition. The present work reports the results of decomposition of DMO on various catalytic materials. The materials studied consist of acidic (γ-Al2O3), basic (MgO), weakly acidic (ZnAl2O4) and neutral surfaces such as α-Al2O3 and mesoporous precipitated SiO2. Infrared spectroscopy is used to identify the nature of adsorption of the molecule on the various surfaces. The spectroscopy study is done at a temperature of 200 °C, which is the onset of gas phase decomposition of DMO. The results indicate that the stability of DMO is lower than the corresponding acid, i.e. oxalic acid. It is also one of the products of decomposition. Spectroscopic data suggest that DMO decomposition is related to surface acidity and the extent of decomposition depends on the number of surface hydroxyl groups. Decomposition was also observed on α-Al2O3, which was attributed to the residual surface hydroxyl groups. DMO decomposition to oxalic acid was not observed on the basic surface (MgO).

Molecularly Imprinted Membranes: Past, Present, and Future.

More than 80 years ago, artificial materials with molecular recognition sites emerged. The application of molecular imprinting to membrane separation has been studied since 1962. Especially after 1990, such research has been intensively conducted by membranologists and molecular imprinters to understand the advantages of each technique with the aim of constructing an ideal membrane, which is still an active area of research. The present review aims to be a substantial, comprehensive, authoritative, critical, and general-interest review, placed at the cross section of two broad, interconnected, practical, and extremely dynamic fields, namely, the fields of membrane separation and molecularly imprinted polymers. This review describes the recent discoveries that appeared after repeated and fertile collisions between these two fields in the past three years, to which are added the worthy acknowledgments of pioneering discoveries and a look into the future of molecularly imprinted membranes. The review begins with a general introduction in membrane separation, followed by a short theoretical section regarding the basic principles of mass transport through a membrane. Following these general aspects on membrane separation, two principles of obtaining polymeric materials with molecular recognition properties are reviewed, namely, molecular imprinting and alternative molecular imprinting, followed the methods of obtaining and practical applications for the particular case of molecularly imprinted membranes. The review continues with insights into molecularly imprinted nanofiber membranes as a promising, highly optimized type of membrane that could provide a relatively high throughput without a simultaneous unwanted reduction in permselectivity. Finally, potential applications of molecularly imprinted membranes in a variety of fields are highlighted, and a look into the future of membrane separations is offered.

Quantification of potential impurities by a stability indicating UV-HPLC method in niacinamide active pharmaceutical ingredient.

A sensitive, stability indicating reverse phase UV-HPLC method has been developed for the quantitative determination of potential impurities of niacinamide active pharmaceutical ingredient. Efficient chromatographic separation was achieved on C18 stationary phase in isocratic mode using simple mobile phase. Forced degradation study confirmed that the newly developed method was specific and selective to the degradation products. Major degradation of the drug substance was found to occur under oxidative stress conditions to form niacinamide N-oxide. The method was validated according to ICH guidelines with respect to specificity, precision, linearity and accuracy. Regression analysis showed correlation coefficient value greater than 0.999 for niacinamide and its six impurities. Detection limit of impurities was in the range of 0.003-0.005% indicating the high sensitivity of the newly developed method. Accuracy of the method was established based on the recovery obtained between 93.3% and 113.3% for all impurities.

Spectrophotometric determination of isoxsuprine hydrochloride using 3-methyl-2-benzothiazolinone hydrazone hydrochloride in spiked human urine and pharmaceuticals.

Two selective and sensitive spectrophotometric methods are proposed for the determination of isoxsuprine hydrochloride (ISX) in spiked human urine and in pharmaceuticals. The methods are based on the oxidative-coupling reaction between 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and ISX in the presence of Ce(SO(4))(2). The novelty of the proposed reaction is the formation of two different colored chromogens at two different pHs. The resulting product at pH<1.5 is a red colored chromogen peaking at 500nm (method A) and that formed between the pH 3.85 and 4.15, is violet colored with an absorption maximum at 580nm (method B). In both the methods, absorbance of the chromogen is found to increase linearly with the concentration of ISX as is corroborated by the correlation coefficients of 0.9989 and 0.9970, and the systems obey Beer's law over the ranges of 1.4-21.0 and 1.0-15.0microgml(-1), for method A and method B, respectively. The calculated molar absorptivities are 1.08 x 10(4) and 1.78 x 10(4)lmol(-1)cm(-1) for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0311 and 0.0190microgcm(-2). The reaction stoichiometry, in both the methods, was evaluated by the limiting logarithmic method and was found to be 1:1 (ISX:MBTH). The methods were successfully applied to the determination of ISX in spiked human urine and pharmaceutical formulation.

Sensitive spectrophotometric assay of simvastatin in pharmaceuticals using permanganate / Ensaio espectrofotométrico sensíveis de sinvastatina em medicamentos utilizando permanganato

Two simple, sensitive, selective and inexpensive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets using permanganate as the oxidimetric reagent. In method A, SMT is treated with a measured excess of permanganate in acetic acid medium and the unreacted oxidant is measured at 550 nm, whereas in method B the reaction is carried out in alkaline medium and the resulting manganate is measured at 610 nm. In method A, the amount of permanganate reacted corresponds to the SMT content and the absorbance is found to decrease linearly with the concentration; and in method B, the absorbance increases with concentration. The working conditions of assays were optimized, and the methods were validated according to the current ICH guidelines. Under optimum conditions, SMT could be assayed in the concentration ranges, 1.47 - 17.67x10-5 and 2.27 - 27.18 x10-6 mol/L by method A and method B, respectively. The calculated molar absorptivities are 3.2 x 10³ and 2.5 x 10(4) L/mol/cm for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0387 and 0.0178 μg/cm². The limits of detection (LOD) and quantification (LOQ) have also been reported. Accuracy and precision for the assay were determined by calculating the intra-day and inter-day at three concentrations; the intra-day RSD was < 2 percent and the accuracy was better than 2.15 percent (RE). The methods were applied successfully for the determination of SMT in tablet dosage form with a high percentage of recovery, good accuracy and precision, and without measurable interference by the excipients. The accuracy was further ascertained from placebo and synthetic mixture analysis and also from the spike-recovery method.

Dois métodos espectrofotométricos simples, sensíveis, seletivos e baratos são descritos para a determinação de sinvastatina (SMT) a granel e em comprimidos, utilizando permanganato como reagente oxidimétrico. No método A, a SMT é tratada com excesso conhecido de permanganato em meio de ácido acético e o oxidante que não reage é medido a 550 nm, enquanto no método B, a reação é efetuada em meio alcalino e o manganato resultante é medido a 610 nm. No método A, a quantidade de permanganato que reage corresponde ao conteúdo de SMT e a absorbância diminui linearmente com o aumento da concentração; no método B, a absorbância aumenta com o aumento da concentração. As condições de trabalho do ensaio foram otimizadas e os métodos, validados de acordo com as normas do ICH. Sob condições ótimas, a SMT pode ser ensaiada nas faixas de concentração de 1,47- 17,67x10-5 e de 2,27-27,18 x10-6 mol/L pelo método A e B, respectivamente. As absortividades molares calculadas são 2 x 10³ e 2,5 x 10(4) L/ mol/cm, respectivamente, para os métodos A e B, com os valores correspondentes de sensibilidade de Sandell de 0,0387 e 0,0178 μg/cm². Os limites de detecção (LOQ) também foram relatados. A exatidão e a precisão do ensaio foram determinadas pelo cálculo de três concentrações intra- e inter-dia; a RSD intra-dia foi <2 por cento e a exatidão foi melhor que 2,15 por cento (RE). Os métodos foram aplicados com sucesso à determinação de SMT em comprimidos com alta porcentagem de recuperação, boa exatidão e precisão e sem interferência mensurável dos excipientes. A exatidão foi posteriormente determinada no placebo e na mistura sintética e, também, pelo método de spike recovery.

Optimized and validated spectrophotometric methods for the determination of raloxifene in pharmaceuticals using permanganate.

Two simple and sensitive spectrophotometric methods are described for the determination of raloxifene hydrochloride (RLX) in pure form and in tablets. The first method (method A) is based on the formation of a yellowish-brown chromogen peaking at 430 nm when RLX was reacted with permanganate in acetic acid medium. In the second method (method B), RLX was reacted with a measured excess of permanganate in H2SO4 medium followed by the spectrophotometric measurement of the unreacted KMnO4 at 550 nm. Under the optimized experimental conditions, Beer's law is obeyed in the concentration range 0.6-6.0 and 1.5-15.0 microg mL(-1) with molar absorptivity of 7.01 x 10(4) and 2.8 x 10(4) L mol(-1) cm(-1) for method A and method B, respectively. The limits of detection (LOD) and quantification (LOQ) have also been reported. The intra-day and inter-day RSD and RE values at three different concentrations were assessed. The proposed methods were applied to the commercially available tablets, and the results were statistically compared with those of the reference method. The accuracy and reliability of the methods were further ascertained by recovery studies.

Gradient HPLC analysis of raloxifene hydrochloride and its application to drug quality control.

A rapid, sensitive and selective method for the determination of raloxifene hydrochloride (RLX) in pure drug and in tablets was developed using gradient high performance liquid chromatography (HPLC). The devised method involved separation of RLX on a reversed phase Hypersil ODS column and determination with UV detection at 284 nm. The standard curve was linear (R = 0.999) over the concentration range of 50-600 microg mL-1 with a detection limit of 0.04 microg mL-1 and a quantification limit of 0.16 microg mL-1. Intra-day and inter-day precision and accuracy of the method were established according to the current ICH guidelines. Intra-day RSD values at three QC levels (250, 450 and 550 microg mL-1) were 0.2-0.5%, based on the peak area. The intra-day relative error (er) was between 0.2 and 0.5%. The developed method was successfully applied to the determination of RLX in tablets and the results were statistically compared with those obtained by a literature method. Accuracy, evaluated by means of the spike recovery method, was the excellent with percent recovery in the range 97.7-103.2 with precision in the range 1.6-2.2%. No interference was observed from the co-formulated substances. The method was economical in terms of the time taken and the amount of solvent used.