Search

A total of 383 tablets of a pharmaceutical product were analyzed by backscatter and transmission Raman spectrometry to determine the concentration of an active pharmaceutical ingredient (API), chlorpheniramine maleate, at the 2% m/m (4 mg) level. As the exact composition of the tablets was unknown, external calibration samples were prepared from chlorpheniramine maleate and microcrystalline cellulose (Avicel) of different particle size. The API peak at 1594 cm(-1) in the second derivative Raman spectra was used to generate linear calibration models. The API concentration predicted using backscatter Raman measurements was relatively insensitive to the particle size of Avicel. With transmission, however, particle size effects were greater and accurate prediction of the API content was only possible when the photon propagation properties of the calibration and sample tablets were matched. Good agreement was obtained with HPLC analysis when matched calibration tablets were used for both modes. When the calibration and sample tablets are not chemically matched, spectral normalization based on calculation of relative intensities cannot be used to reduce the effects of differences in physical properties. The main conclusion is that although better for whole tablet analysis, transmission Raman is more sensitive to differences in the photon propagation properties of the calibration and sample tablets.

Particle size distribution and compactness have significant confounding effects on Raman signals of powder mixtures, which cannot be effectively modeled or corrected by traditional multivariate linear calibration methods such as partial least-squares (PLS), and therefore greatly deteriorate the predictive abilities of Raman calibration models for powder mixtures. The ability to obtain directly quantitative information from Raman signals of powder mixtures with varying particle size distribution and compactness is, therefore, of considerable interest. In this study, an advanced quantitative Raman calibration model was developed to explicitly account for the confounding effects of particle size distribution and compactness on Raman signals of powder mixtures. Under the theoretical guidance of the proposed Raman calibration model, an advanced dual calibration strategy was adopted to separate the Raman contributions caused by the changes in mass fractions of the constituents in powder mixtures from those induced by the variations in the physical properties of samples, and hence achieve accurate quantitative determination for powder mixture samples. The proposed Raman calibration model was applied to the quantitative analysis of backscatter Raman measurements of a proof-of-concept model system of powder mixtures consisting of barium nitrate and potassium chromate. The average relative prediction error of prediction obtained by the proposed Raman calibration model was less than one-third of the corresponding value of the best performing PLS model for mass fractions of barium nitrate in powder mixtures with variations in particle size distribution, as well as compactness.

Large-scale commercial bioprocesses that manufacture biopharmaceutical products such as monoclonal antibodies generally involve multiple bioreactors operated in parallel. Spectra recorded during in situ monitoring of multiple bioreactors by multiplexed fiber-optic spectroscopies contain not only spectral information of the chemical constituents but also contributions resulting from differences in the optical properties of the probes. Spectra with variations induced by probe differences cannot be efficiently modeled by the commonly used multivariate linear calibration models or effectively removed by popular empirical preprocessing methods. In this study, for the first time, a calibration model is proposed for the analysis of complex spectral data sets arising from multiplexed probes. In the proposed calibration model, the spectral variations introduced by probe differences are explicitly modeled by introducing a multiplicative parameter for each optical probe, and then their detrimental effects are effectively mitigated through a "dual calibration" strategy. The performance of the proposed multiplex calibration model has been tested on two multiplexed spectral data sets (i.e., MIR data of ternary mixtures and NIR data of bioprocesses). Experimental results suggest that the proposed calibration model can effectively mitigate the detrimental effects of probe differences and hence provide much more accurate predictions than commonly used multivariate linear calibration models (such as PLS) with and without empirical data preprocessing methods such as orthogonal signal correction, standard normal variate, or multiplicative signal correction.

A novel method has been devised to derive kinetic information about reactions in microfluidic systems. Advantages have been demonstrated over conventional procedures for a Knoevenagel condensation reaction in terms of the time required to obtain the data (fivefold reduction) and the efficient use of reagents (tenfold reduction). The procedure is based on a step change from a low (e.g., 0.6 μL min(-1)) to a high (e.g., 14 μL min(-1)) flow rate and real-time noninvasive Raman measurements at the end of the flow line, which allows location-specific information to be obtained without the need to move the measurement probe along the microreactor channel. To validate the method, values of the effective reaction order n were obtained employing two different experimental methodologies. Using these values of n, rate constants k were calculated and compared. The values of k derived from the proposed method at 10 and 40 °C were 0.0356 ± 0.0008 mol(-0.3) dm(0.9) s(-1) (n = 1.3) and 0.24 ± 0.018 mol(-0.1) dm(0.3) s(-1) (n = 1.1), respectively, whereas the values obtained using a more laborious conventional methodology were 0.0335 ± 0.0032 mol(-0.4) dm(1.2) s(-1) (n = 1.4) at 10 °C and 0.244 ± 0.032 mol(-0.3) dm(0.9) s(-1) (n = 1.3) at 40 °C. The new approach is not limited to analysis by Raman spectrometry and can be used with different techniques that can be incorporated into the end of the flow path to provide rapid measurements.

International audience; There is an increasing interest in using Raman spectroscopy to identify polymorphic forms and monitor phase changes in pharmaceutical products for quality control. Compared with other analytical techniques for the identification of polymorphs such as X-ray powder diffractometry and infrared spectroscopy, FT-Raman spectroscopy has the advantages of enabling fast, in situ, and nondestructive measurements of complex systems such as suspension samples. However, for suspension samples, Raman intensities depend on the analyte concentrations as well as the particle size, overall solid content, and homogeneity of the solid phase in the mixtures, which makes quantitative Raman analysis rather difficult. In this contribution, an advanced model has been derived to explicitly account for the confounding effects of a sample's physical properties on Raman intensities. On the basis of this model, a unique calibration strategy called multiplicative effects correction (MEC) was proposed to separate the Raman contributions due to changes in analyte concentration from those caused by the multiplicative confounding effects of the sample's physical properties. MEC has been applied to predict the anhydrate concentrations from in situ FT-Raman measurements made during the crystallization and phase transition processes of citric acid in water. The experimental results show that MEC can effectively correct for the confounding effects of the particle size and overall solid content of the solid phase on Raman intensities and, therefore, provide much more accurate in situ quantitative predictions of anhydrate concentration during crystallization and phase transition processes than traditional PLS calibration methods.

Two novel methods are described for direct quantitative analysis of NMR free induction decay (FID) signals. The methods use adaptations of the generalized rank annihilation method (GRAM) and the direct exponential curve resolution algorithm (DECRA). With FID-GRAM, the Hankel matrix of the sample signal is compared with that of a reference mixture to obtain quantitative data about the components. With FID-DECRA, a single-sample FID matrix is split into two matrices, allowing quantitative recovery of decay constants and the individual signals in the FID. Inaccurate results were obtained with FID-GRAM when there were differences between the frequency or transverse relaxation time of signals for the reference and test samples. This problem does not arise with FID-DECRA, because comparison with a reference signal is unnecessary. Application of FID-DECRA to 19F NMR data, which contained overlapping signals from three components, gave concentrations comparable to those derived from partial least squares (PLS) analysis of the Fourier transformed spectra. However, the main advantage of FID-DECRA was that accurate (5% error) and precise (2.3% RSD) results were obtained using only one calibration sample, whereas with PLS, a training set of 10 standard mixtures was used to give comparable accuracy and precision.

Factors that affect quantitative analysis by surface-enhanced resonance Raman scattering (SERRS) have been investigated using azobenzotriazol and reactive dyes. Preaggregation of the silver colloid was the most effective method to obtain repeatable and reproducible scattering. Aggregation by poly(l-lysine) or spermine provided better precision than aggregation by sodium chloride or nitric acid. Repeatable quantitative analysis was achieved with the azobenzotriazol dyes. A linear calibration graph was obtained over different concentration ranges below 10(-)(8) M, depending on the nature of the colloid. Calculations estimate that 10(-)(8) M is the concentration at which monolayer coverage of the dye on the silver colloid is achieved. Above 10(-)(8) M, there was only a minor increase in the scattering intensity from the azobenzotriazol dyes. In contrast, the reactive dyes did not give a response proportional to concentration over the range studied. The different responses obtained for the two types of dye are believed to be caused by differences in the nature of the interaction of the molecules with the silver surface. The conclusion reached is that control of the colloid preparation, aggregation process, and surface chemistry are essential for successful quantitative analysis of dyes on colloidal silver by SERRS.

Infrared (IR) remote sensors calibrated with propane understate volatile organic compound (VOC) concentrations in vehicle exhaust by 30−70% when compared to flame ionization detectors (FID). The difference depends on VOC composition and arises because many organic compounds in vehicle exhaust absorb less IR radiation than propane on a per-carbon basis. This study demonstrates an approach for scaling infrared measurements to reflect more accurately total exhaust VOC emissions from on-road motor vehicle fleets. Infrared versus flame ionization detector response to individual VOC was measured in the laboratory for methyl tert-butyl ether and a range of alkanes, alkenes, and aromatics that are prominent in vehicle exhaust. Overall IR/FID response to real exhaust mixtures was calculated by summing the response contributions of all individual VOC constituents. Average IR/FID response factors were calculated for typical on-road vehicle fleets based on VOC speciation profiles measured in several U.S. roadway tunn...

Wet flue gas desulfurization scrubbers can be retrofitted for combined removal of SO 2 and NO x from flue gas by adding a newly developed iron(II) thiochelate to limestone slurries. This additive enhances the solubility of NO in limestone slurries by binding NO to form iron nitrosyl thiochelates. The bound NO is then converted to an ammonium ion by iron metal, regenerating the active iron(II) catalyst for continued NO capture. The conditions of the chemical regeneration of iron(II) thiochelate have been studied. This chemical reduction method is efficient, simple, and cost-effective. Integrated tests of this new iron additive on a bench-scale system have been conducted. A turbulent contact absorber was employed to test simultaneous removal of NO and SO 2 with iron(II) thiochelate in a limestone slurry. The steady-state NO removal efficiency depends on the operating conditions of an absorber, the iron chelate concentration, the fraction of the flow diverted for regeneration, and the conditions used in the regeneration reactor. The bench-scale test results were used to develop a prediction of the performance of a full-scale spray absorber.

Nitrous acid (HONO) is an important tropospheric air pollutant. Photolysis of HONO produces hydroxyl radicals that promote ozone formation. HONO may also adversely affect human health. Sources of HONO include both direct emission from combustion processes and secondary atmospheric formation from nitrogen oxides (NOx). The relative contribution of these sources to ambient HONO concentrations is not well known. In this study, HONO and NOx emissions from on-road vehicles were measured at the Caldecott Tunnel during summer 1995. The Caldecott Tunnel is located on a heavily used highway in the San Francisco Bay area. The mean and median model years of vehicles observed during this study were 1989.3 and 1990, respectively. Nitrous acid was collected on sodium carbonate-coated glass annular denuders; NOx concentrations were measured using chemiluminescent analyzers. Average HONO concentrations in the tunnel exhaust and background air were 6.9 ± 1.4 and 0.7 ± 0.3 ppb, respectively. The average HONO/NOx ratio in m...

The iron(II) bis(2,3-dimercapto-1-propanesulfonate) (Fe2+(DMPS)2) complex is a newly developed metal thiochelate for the removal of NOx from flue gas. The mass transfer and kinetics of the absorption of NO in aqueous Fe2+(DMPS)2 solutions have been studied in a stirred reactor. Factors influencing the NO absorption rate, such as pH, Fe2+(DMPS)2 concentration, and the ratio of Fe2+ to DMPS have been investigated. The forward rate constant of the Fe2+(DMPS)2−NO complexation reaction has been determined to be 1.1 × 108 L/mols at pH 7.2 and 50 °C.

The oxidative decomposition of nitrogen-sulfur oxides, formed by the reaction of nitrite ion and hydrogen sulfite ion in aqueous solution, has been investigated. The oxidants used in this study included hydrogen peroxide, nitrogen dioxide, and ozone. There was a wide range of susceptibility to oxidation among the compounds studied. Ozone was a better oxidant than nitrogen dioxide and hydrogen peroxide under the conditions used. The rate expression for the reaction of hydrogen peroxide with hydroxylamine was found to be -d[H[sub 2]O[sub 2]]/dt = k [H[sub 2]O[sub 2]] [NH[sub 2]OH], where k = (7.3 [+-] 0.5) [times] 10[sup [minus]4] M[sup [minus]1] s[sup [minus]1] at 25 C.

The reaction of nitrogen dioxide with aqueous sulfite solutions, in the presence and in the absence of oxygen, has been studied using Raman spectroscopy to determine product concentrations. The products observed include nitrite, sulfate, and dithionate ions. The reaction appears to initially produce nitrite ion and sulfite radical: NO 2 +SO 3 2- →NO 2 - +SO 3 .- . The sulfite radical can undergo either recombination or reaction with oxygen to form SO 5 .

This paper reports on the influence of anions and cations commonly found in flue gas scrubber systems on the hydrolysis rate of disulfate ion (S{sub 2}O{sub 7}{sup 2{minus}}) that has been studied. The cations studied include Na{sup +}, K{sup +} Ca{sup 2+}, Mg{sup 2+}, and Mn{sup 2+}. The anions studied include SO{sub 3}{sup 2{minus}}, SO{sub 4}{sup 2{minus}}, S{sub 2}O{sub 3}{sup 2{minus}}, S{sub 2}O{sub 6}{sup 2{minus}}, HSO{sub 3}{sup {minus}}, Cl{sup {minus}}, H{sub 2}PO{sub 4}{sup {minus}}, and HPO{sub 4}{sup 2{minus}}. Of the ions studied, Ca{sup 2+}, Mg{sup 2+}, SO{sub 3}{sup 2{minus}}, and S{sub 2}O{sub 6}{sup 2{minus}} were found to approximately double the rate of S{sub 2}O{sub 7}{sup 2{minus}} hydrolysis. Adipic acid was found to have no effect on S{sub 2}O{sub 7}{sup 2{minus}} hydrolysis. Activation energies for the S{sub 2}O{sub 7}{sup 2{minus}} hydrolysis rate accelerated by Ca{sup 2+}, Mg{sup 2+}, and SO{sub 3}{sup 2{minus}}, as well as for the unenhanced rate, were found to be in the range of 9-12 kcal/mol.

The chemistry of wet limestone flue gas desulfurization (FGD) systems is complicated by the interaction of dissolved SO 2 and dissolved nitrogen ocides. A substantial number of nitrogen-sulfur compounds can be formed from the reactions of sulfite and bisulfite ions with nitrogen oxyanions. A computer model is used to simulate the kinetics and to determine the effect of scrubber operating conditions on the production of nitrogen-sulfur compounds. With increasingly stringent regulations covering solid and liquid waste disposal, it is important to minimize undesirable byproducts in FGD systems. The modeling is also used to study the effect of scrubber conditions on the production of N 2 O (nitrous oxide). Emission of N 2 O into the atmosphere is undesirable because it has both significant ozone depletion potential and global warming potential

Treatment of water-soluble carboxylic acids with concentrated hydrogen peroxide generates solutions of peracids. These compounds can rapidly oxidize NO x and SO 2 to their respective oxyanions, making them useful in flue gas treatment. The properties of performic acid, peracetic acid, and perpropionic acid are reported and are compared with peroxymonosulfuric acid. The chemistry of NO x and SO 2 removal by these compounds is discussed

The reaction of ferrous chelate nitrosyl complexes with sulfite and bisulfite ions has been studied, and a mechanism for the reaction has been developed

The kinetics of the reaction of dissolved nitric oxide with sulfite and bisulfite ions was studied over a pH range of 4-10 by monitoring the reaction product, N-nitrosohydroxylamine-N-sulfonate (NHAS), with rapid-mixing, continuous-flow and stopped-flow systems. The kinetics of the reaction can be described as d(NHAS)/dt = k/sub a/(NO)(HSO/sub 3//sup -/) + k/sub a/(NO)(SO/sub 3//sup 2 -/) where k/sub a/ = 32 +/- 10 M/sup -1/ s/sup -1/ and k/sub b/ = 620 +/- 100 M/sup -1/ s/sup -1/ at T = 298 K. The reaction was also studied at 284 and 323 K. The hydrolysis rate of NHAS was determined over a pH range of 4-6.

Etude de l'oxydation de l'ion bisulfite, avec formation d'un intermediaire S 2 O 7 2− qui s'hydrolyse en SO 4 2− , H + et/ou HSO 4 2−

It has been suggested (Yaverbaum, 1979) that Fe /SUP II/ EDTA can be an effective binding reagent/additive for NO in wet simultaneous flue gas desulfurization and denitrification scrubbers. The equilibrium constant of the reaction of NO with Fe /SUP II/ EDTA to form Fe /SUP II/ (EDTA)NO (Hishinuma et al., 1979) is about a factor of 2 larger than that with Fe /SUP II/ NTA to form Fe /SUP II/ (NTA)NO at a typical wet scrubber temperature, T = 50 /sup 0/C. However, NTA is less expensive than EDTA. The rate of binding of NO to form nitrosyl ferrous complexes by both Fe /SUP II/ NTA and Fe /SUP II/ EDTA is probably within the same order of magnitude and is much faster compared with the mass transfer rate at typical wet scrubber conditions. Determining the rate of regeneration of these metal chelates by investigating the kinetics of the reaction of Fe /SUP II/ (NTA)NO and Fe /SUP II/ (EDTA)NO with absorbed SO/sub 2/ in aqueous solutions is important for assessing whether NTA or EDTA is an optimum chelating agent.

Ion chromatography was used in the determination of hydroxyimidodisulfate, hydroxysulfamate, imidodisulfate, and N-nitrosohydroxylamine-N-sulfonate compounds. Bicarbonate (1.5 mM) was used as an eluent with a standard separation column for separation of the singly charged anions. Carbonate (12 or 18 mM) was used as an eluent with a short separation column for separation of the doubly charged anions. The detection limits for these compounds were as follows: hydroxyimidodisulfate, 7.4 x 10/sup -6/ M; hydroxysulfamate, 0.5 x 10/sup -6/ M; imidodisulfate, 1.4 x 10/sup -6/ M; and N-nitrosohydroxylamine-N-sulfonate, 14 x 10/sup -6/ M. Ion chromatography was found to have an advantage in speed and sensitivity compared to other determination methods. 11 references, 5 figures.

The ferrous ion to nitric oxide ratio has been determined for the class of compounds Fe/sup II/(L)/sub x/(NO)/sub y/, where L = H/sub 2/O, citrate, IDA, NTA, and EDTA. All compounds studied were found to have a maximum ferrous ion to nitric oxide ratio of 1:1. In addition, the equilibrium constant for the binding of nitric oxide to Fe/sup II/(H/sub 2/O)/sub 6/ was determined to be 470 M/sup -1/ at pH 3 and 25/sup 0/C. The compounds have been proposed as agents to aid in the removal of nitric oxide from power plant flue gas streams.

A number of nitrogen sulfonates are produced by reactions between bisulfite ions and nitrite ions in aqueous solution. Thus, their chemistry is of interest in studies of aqueous aerosols in polluted air and in wet flue gas scrubbing systems. The hydrolysis reactions of nitridotrisulfate (NTS) and hydroxysulfamate (HSA), have been thoroughly investigated. Sisler and Audrieth observed the hydrolysis reaction of NTS at several temperatures: N(SO/sub 3/)/sub 3//sup 3 -/ + H/sub 2/O ..-->.. HN(SO/sub 3/)/sub 2//sup 3 -/ + H/sup +/ + SO/sub 4//sup 2 -/. They found that the NTS hydrolysis reaction occurred much more quickly than the iminodisulfate hydrolysis reaction but did not obtain any quantitative results. The authors have studied the hydrolysis of NTS over a temperature range of 283-333 K at solution pHs ranging from 4.1 to 6.7. The influence of ionic strength was determined over a range of ..mu.. = 0.03-0.5 M.