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NMR diffusometry is a powerful but challenging method to analyze complex mixture. Each component diffuses differently, from the faster small species to the slower large species, corresponding to different signal attenuation. However, the method is highly sensitive to the quality of the acquired data and the performance of the processing used to resolve multiexponential signals influences. Adapting the signal decay sampling to the mixture composition is one way to improve the precision of the measure. In this work, we propose a prediction tool, based on the calculation of the Cramér-Rao lower bound to minimize the variance of diffusion coefficient estimation in order to determine the optimal number of diffusion gradient steps, the best diffusion gradient sampling (among linear, exponential, quadratic and sigmoidal ones) and the optimal maximum diffusion factor. The tool was validated experimentally on a unimer/micelle solution of sodium dodecyl sulfate and on Caelyx ® , a commercial liposomal preparation containing a mixture of pegylated-liposomes and sucrose., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Headspace solid phase microextraction (HSSPME) of chemically generated selenium hydride from alkaline solution followed by thermal desorption (TD) coupled directly to a microwave plasma (MWP) source has been examined for the optical emission spectrometric (OES) determination of Se. Various chemical and operating parameters including the NaBH(4) and HCl concentrations as well as the fiber exposure time and desorption temperature have been optimized. Alternatively, continuous hydride generation (HG) from alkaline medium and inductively coupled plasma (ICP) may be used for Se determination by OES. With the procedure developed, the determination of Se in dietary supplements at the tens of μgg(-1) level and an accuracy of 3-6% could be performed even in the presence of the 1000-fold excess of Fe and Cu. Additionally, Se was determined in the NIST 8418 material (Wheat gluten) with a certified concentration of Se of 2.58 ± 0.19 μgg(-1), and a value of 2.45 ± 0.25 μgg(-1) was found using HG-HSSPME-MWP-OES. The detection limit for Se (3.2 ng ml(-1)) with the proposed procedure was comparable to those obtained with HG-ICP-OES and the calibration curve was linear of about 2 orders of magnitude., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A mid-infrared transmission spectroscopic method with the possibility of high sample throughput was developed and validated on the basis of GMP requirements for protein therapeutics. In comparison with the method predominantly used, i.e. the surface-sensitive attenuated total reflection (ATR), we have shown that transmission measurements in solution possess several advantages, such as quantitative analysis on the basis of Lambert-Beer's law, determination of identity and purity based on specifically developed identity criteria, characterization of protein structure and structural changes including aggregation in solution and study of ligand binding to the protein. The usefulness of this method is exemplified by the characterization of the drug substance of ONCOHIST (recombinant human histone H1.3 and bis-Met-histone H1.3) and its interaction with phosphate ions. Our conclusion is that transmission mid-infrared spectroscopy is a powerful tool for protein analysis in biotechnology and supplements the current analytical techniques for biopharmaceutical quality control of therapeutic proteins., (Copyright 2010. Published by Elsevier B.V.)

A rapid method for simultaneous determination of main phenolic acids in Radix Salvia Miltrorrhiza extract solutions was developed using Fourier transform near infrared spectroscopy in transflective mode and multivariate calibration and HPLC-UV as the reference method. Partial least squares (PLS) algorithm was conducted on the calibration of regression models. The multiplicative scatter correction, Norris derivative and second derivative were adopted for the spectral pre-processing, and the number of PLS factors were optimized by leave-one-out cross-validation. The performance of the final model was evaluated according to root mean square error of prediction (RMSEP) and correlation coefficient (R). The R values achieved in the prediction set were above 0.93. The developed models were used for analysis of unknown samples and routine monitoring with satisfactory results. This work demonstrated that NIR spectroscopy combined with PLS algorithm could be used for the rapid determination of the main phenolic acids of Salvia Miltrorrhiza extract solutions., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Ultrasonic wave reflection coefficients of aqueous solutions were measured using high-impact polystyrene as a buffer material to provide enhanced sensitivity over metal or ceramic buffer materials. The wave reflection values showed linear reduction when the concentration of chemical species in solution was increased, but a distinct relation between concentration and reflection coefficient was obtained for each solute species tested. However, more unified relationships were observed between reflection coefficient and other solution parameters - solution density, acoustic impedance, and P-wave velocity - that were consistent for all solution species. Based on this behavior an expression to compute solution density solely from reflection coefficient is derived, which can be applied to estimate solution density in solutions of unknown solute species and concentration when other measurements, such as wave velocity, are not possible.

The quantitative resolution of a quaternary pharmaceutical mixture consisting of paracetamol, propiphenazone, caffeine and thiamine was performed by the simultaneous use of fractional wavelet transform (FWT) with principal component regression (PCR), partial least squares (PLS) and artificial neural networks (ANN) methods. A calibration set consisting of 22 mixture solutions was prepared by means of an orthogonal experimental design and their absorption spectra were recorded in the spectral range of 210.0-312.3nm and then transferred into the fractional wavelet domain and processed by FWT. The chemometric calibrations FWT-PCR, FWT-PLS and FWT-ANN were computed by using the relationship between the coefficients provided by FWT method and the concentration data from calibration set. An external validation was carried out by applying the developed methods to the analysis of synthetic mixtures of the related compounds, obtaining successful results. The models were finally used to assay the studied drugs in the commercial pharmaceutical formulations.

A method for sample preparation and high-performance liquid chromatography detection and quantification has been developed for the routine analysis of psoralen and bergapten, photosensitizing compounds, in topic solutions employed in Brazil for treatment of vitiligo and psoriasis. The linearity, accuracy, the inter- and intra-day precision of the procedure were evaluated. The calibration curve for psoralen and bergapten were linear in the range 1.0-20.0 microg ml(-1). The best recoveries of the psoralens in the topic solutions analysed were 96.3-98.2%. The percentage coefficient of variation of the quantitative analysis of the psoralens in the product analyses was within 5%.

A coated-wire benazepril-selective electrode based on incorporation of the benazepril-tetraphenylborate ion pair in a poly(vinylchloride) coating membrane was constructed. The influences of membrane composition, temperature, pH of the test solution, and foreign ions on the electrode performance were investigated. The electrode showed a Nernstian response over a benazepril concentration range of 1.26x10(-5) to 0.58x10(-2) M, at 25 degrees C, and was found to be very selective, precise, and usable within the pH range 2.5-9.2. The standard electrode potentials, E degrees, were determined at 20, 25, 30, 35, 40 and 45 degrees C, and used to calculate the isothermal temperature coefficient (dE degrees /dT) of the electrode. Temperatures higher than 45 degrees C seriously affect the electrode performance. The electrode was successfully used for potentiometric determination of benazepril hydrochloride both in pure solutions and in pharmaceutical preparations.

Objectives: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage., Methods: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After 14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were analyzed for heavy-metal deposition by using inductively coupled plasma mass spectrometry. Tissues were fixed in formalin, sectioned, and stained with hematoxylin and eosin, periodic acid Schiff, and Masson's trichrome stain. Kidneys were fixed in gluteraldehyde for ultrastructural examination with scanning electron microscopy., Results: The predominant sources of contaminants in TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca gluconate (Al), K2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As). Significant variations in the level of contamination depended on TPN formulation and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were greater than in controls, although there was no correlation with serum creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although there was no correlation with serum aspartate aminotransferase or total bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN rats. Only serum Cr concentration was significantly correlated with splenic concentration (r = 0.46, P = 0.04). Brain and serum Ba concentrations were significantly correlated (r = 0.60, P = 0.007). No significant correlations were observed between any other metal in serum and that metal's respective organ concentration. No increase in heavy-metal accumulation was seen in the femur, spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V in any of the organs examined. Serum Al and Cr concentrations were significantly increased in TPN rats, although there was no correlation with tissue concentrations. No significant increases in heavy-metal concentrations in tissue or plasma were observed for any of the other metals measurable by inductively coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the rats had mild to moderate hepatic steatosis and 33% to 50% developed renal morphologic abnormalities; brains and spleens remained histologically normal., Conclusions: We found significant heavy-metal contamination of TPN solutions, and this contamination can lead to organ deposition and subsequent histologic abnormalities.

Contamination of parenteral nutrition solutions with aluminum may result in accumulation of this element in bones and, in premature infants, may inhibit bone calcium uptake and induce cholestasis. We measured the aluminum concentration of small-volume parenterals, amino acid solutions, lipid emulsions, and special solutions containing glucose, amino acids, electrolytes, and trace elements (standard I for children with a body weight of 3-5 kg, standard II for children with a body weight of 5-10 kg). The method used was graphite furnace atomic absorption spectrometry GTA-AAS (SpectrAA-400 Plus, Varian, PtY Ltd., Mulgrave, Australia). Quality control was run with the use of control serum (Seronorm, Nycomed, Oslo, Norway). The aluminum contents of parenterally administered solutions were: pediatric trace elements, 130 micrograms/L, and pediatric trace elements, 3000 micrograms/L; phosphorus salts: K-phosphates, 9800 micrograms/L, and Na/K phosphates, 13,000 micrograms/L; 10% calcium gluconate, 4400 micrograms/L; 6.5% amino acids, 30 micrograms/L; 10% amino acids, 120 micrograms/L; 12.5% amino acids, 121 micrograms/L; 20% lipid emulsion, 30 micrograms/L; 20% lipid emulsion, 180 micrograms/L; water-soluble vitamins, 12 micrograms/L; lipid soluble vitamins, 360 micrograms/L; standard I, 55 micrograms/L; standard II, 90 micrograms/L; The aluminum intake from parenteral nutrition was 6.6-10.8 micrograms.kg-1.d-1--a dose exceeding the safety limit of 2 micrograms.kg-1.d-1. The possible association of aluminum not only with metabolic bone disease, but also with encephalopathy, dictates caution when dealing with the pediatric population on long-term parenteral nutrition. In the absence of reliable label information, it seems proper to monitor the aluminum concentration in parenteral nutrition products and to report it in professional journals.

A sensitive and fast flow-injection spectrophotometric method for the determination of diclofenac sodium based on the formation of coloured compound with Ce(IV)-3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in H2SO4 3 x 10(-2) M medium is proposed. Using the peak height as a quantitative parameter diclofenac was determined at 580 nm over the range 0.20-8.0 micrograms ml-1. The proposed method was successfully applied to the determination of diclofenac in pharmaceuticals and urine samples.

A voltammetric method has been developed for the determination of metronidazole in dosage forms. The method is based on the electrochemical reduction of the drug at a glassy carbon electrode activated by applying a new pretreatment. The influence of pH, concentration, scan rate and presence of organic solvent and surfactant has been studied. The current is proportional to the concentration and permits the drug to be determined in the concentration range 2 x 10(-6)-6 x 10(-4) M in Britton-Robinson buffer (pH 10). Furthermore, results obtained by the proposed method have been compared with USP XXIII procedure which involves a HPLC method.

Two capillary zone electrophoretic assays using run buffers of pH 9.35 and pH 2.70 have been developed for the determination of aspartame (alpha-L-Asp-L-PheOMe) and its potential degradation products including Phe, PheOMe, 5-benzyl-3,6-dioxo-2-piperazineacetic acid (DKP), the dipeptides Asp-Phe and Phe-Asp, as well as the isomeric beta-aspartame (beta-L-Asp-L-PheOMe). As an uncharged species at pH 2.7 DKP could not be determined. Between pH 2.0 and 3.5 the resolution of the diastereomers of aspartame and beta-aspartame was investigated. While the resolution of the epimeric beta-isomers exhibited a plateau between pH 2.3 and 2.7, resolution of the aspartame diastereomers peaked at pH 3.0. Using salicylic acid and Phe-Gly as internal standards at pH 9.35 and 2.70, respectively, linear calibration curves were obtained for a concentration range between 5 micrograms ml-1 and 1 mg ml-1. The R.S.D. for intraday and interday analysis ranged from 1.0 to 3.6% and 1.5% to 9.1%, respectively. The capillary electrophoresis assays were applied to analyze aspartame solutions heated to 70 degrees C. In agreement with the literature data aspartame was found to be less stable at pH 7 compared to pH 3. In contrast to aspartame itself, an approximate 20% epimerization of beta-aspartame was observed in the incubation mixtures.

A sensitive spectrophotometric assay has been developed for the determination of methoxamine in pure dosage form and in its pharmaceutical preparations. The method is based on the acidic oxidation of methoxamine with cerium(IV) in the micellar medium of sodium lauryl sulphate at 96 degrees C. The reaction yields a water-soluble purple product which can be quantified spectrophotometrically at 505 nm. The calibration curve was linear between 1.0 and 20 micrograms ml-1 with a limit of detection 0.5 microgram ml-1. The molar absorptivity at 505 nm is 8.3 X 10(3) iota mol-1 cm-1. The method is simple and rapid since the product is measured directly in solution without extraction.

Rapid, simple and direct assay procedures based on selective first (D1)- and second (D2)-derivative spectrophotometry, using a zero-crossing technique of measurement at 279.2 and 280.0 nm, respectively, have been developed for the specific determination of guaiphenesin in the presence of dextromethorphan, drugs with closely overlapping absorption spectra, in synthetic admixtures and in pharmaceutical dosage forms (tablets and syrups). The methods do not require extraction with organic solvents and are easier to perform than their conventional counterparts. Calibration graphs were linear (r = 0.99999 for D1 and 0.99969 for D2, respectively). Good selectivity, accuracy and precision were found. However, the performance of the analysis of guaiphenesin by the second-derivative mode deteriorated when the ratio of dextromethorphan to guaiphenesin was greater than one. Thus, the first-derivative spectrophotometry is the method of choice for the assay of tablets and syrups containing the two drugs.

A general construction procedure for conventional shape ion-selective electrodes based on a conductive support prepared with a mixture of a non-conductive epoxy and graphite was used in the preparation of a flow-through benzoate electrode to be used as potentiometric detector in flow injection analysis manifolds. The membranes were prepared from tetraoctylammonium benzoate in o-nitrophenyloctylether immobilized on PVC. The results of the assessment of the tubular electrodes behaviour in low dispersion manifolds against that of conventional electrodes with the same membrane are reported. Data obtained with a double-channel flow injection manifold incorporating these tubular detectors for benzoate determinations in several commercially available pharmaceutical preparations are also presented.