Determination of trace perchlorate in river water by ion chromatography with online matrix removal and sample concentration.

This paper proposes a simple ion chromatographic approach to determine trace amounts of perchlorate in river water samples. Determination of the trace perchlorate by ion chromatography typically faces two challenges: interference by matrix ions such as chloride, nitrate, and sulfate in the samples and insufficient detection sensitivity. In the present study, online pretreatment of the samples with an OnGuard II Ba/Ag/H disposable sample pretreatment cartridge prevented the sulfate peak tailing from overlapping with the perchlorate peak on the chromatogram. In addition, the matrix removal enabled as large as 10 mL of sample to be loaded into a high exchange capacity anion concentrator, significantly improving perchlorate's detection sensitivity. The proposed approach achieved a detection limit (S/N = 3) of 0.046 µg L-1 without using a costly mass spectrometer and successfully determined sub µg L-1 levels of perchlorate in river water.

Integrated continuous flow method with dual feedback-based controls for online analysis and process control.

The concept of an integrated automated continuous flow method with dual feedback controls is presented for diluting a stock solution to provide a solution of a given concentration. The one control is used for the online process monitoring by a feedback-based flow ratiometry, where the product (the diluted liquid) is titrated through the rapid bidirectional scan of the product/reagent flow ratio. The feedback control limits the scanning to the necessary range to increase the analytical throughput. The other control is used for the process control to output the product with a preset concentration. The merging ratio of the stock solution and a solvent (diluent) is changed based on the information from the online analysis. The concept was verified by applying it to producing 0.1 mol dm-3 CH3COOH. When the stock concentration was changed from 0.1 (reference concentration) to 0.3 and then 0.2 mol dm-3, the system searched for the suitable merging ratio and converged the output concentration to the reference value within 7.43 min with a relative error below 1.05%. The mean throughput rate of the process analysis was 11.2 titrations min-1. Successful results were also obtained for the 0.1 mol dm-3 HCl production. The present concept could be the basis for process control with reduced wasteful output and effluent treatment with eco-friendly treated water discharge, resulting in the contribution to SDGs' goals of 6 (Clean water and sanitation), 9 (Industry, innovation and infrastructure), and 14 (Life below water).

Inner product of RGB unit vectors for detecting color transition: application to feedback-based flow ratiometric titration.

The inner product (IP) of RGB unit vectors' approach for detecting color transition has further been applied to a feedback-based flow ratiometric titration, including nonaqueous titration. While the flow ratio of titrand/titrant containing an indicator was varying, the video image of the merged solution was taken with a digital microscope downstream. The indicator's color was converted to an RGB unit vector. The change in IP between vectors was used for determining the equivalence point. The concept was successfully applied to the determinations of drug and vinegar samples with reasonable throughput rate (> 18 s/titration) and precision (RSD < 4.4%).

Triangular-wave controlled amplitude-modulated flow analysis for extending dynamic range to saturated signals.

We have applied our amplitude-modulated flow analysis concept to extend the dynamic range to saturated analytical signals. Sample solution, the flow rate FS of which is periodically varied with a triangular control signal Vc, is merged with a reagent solution delivered at a constant flow rate FR. While the total flow rate FT is kept constant, a diluent with FT-(FS + FR) flow rate is aspirated from the third channel. The analytical signal Vd obtained downstream is processed by fast Fourier transform to obtain the amplitudes of the wave components in Vd. When the sample concentration CS is low, Vd shows a triangular profile like Vc; the sum of the amplitudes ΣA is proportional to CS. When CS is high, Vd shows a trapezoidal profile because of the Vd saturation. A linear calibration curve can also be obtained for such saturated signals by plotting CSΣA against CS. The proof of the concept is validated by applying it to spectrophotometric determinations of a dye (Methylene Blue) and colored complexes of Fe2+ - phenanthroline and Fe3+ - Tiron.

Inner Product of RGB Unit Vectors for Simple and Versatile Detection of Color Transition.

We propose a novel concept for detecting color transition by the inner product (IP) of RGB unit vectors. A digital microscope-based detector and a Visual Basic program were developed in-house. The concept is applied to indicator-based flow titration. The IP is 1 or < 1 if the vector's direction is the same or different, respectively. The IP's change can be used as a criterion for the indicator's color transition. The present IP-based approach is simple, economical, and versatile because it is applicable to any color transition without selecting an analytical wavelength.

Predictive evaluation of powder X-ray diffractograms of pharmaceutical formulation powders based on infrared spectroscopy.

BACKGROUND: To ensure quality and stability, monitoring systems are recommended to analyze pharmaceutical manufacturing processes. OBJECTIVE: This study was performed to predict powder X-ray diffraction (PXRD) patterns of formulation powders through attenuated total reflectance (ATR)-infrared (IR) spectroscopy in a nondestructive manner along with chemometrics. RESULTS: Caffeine anhydrate, acetaminophen, and lactose monohydrate were grinded at six weight ratios. The six sample groups were evaluated using ATR-IR spectroscopy and PXRD analysis. Partial least squares models were constructed to predict the PXRD intensities of the samples from the ATR-IR spectra. The prediction accuracy on the prepared PLS regression models was as high as R2 = 0.993. CONCLUSIONS: Linear relationships were obtained between the prediction data set and reference PXRD intensity at each degree. 2D PLS regression coefficient analysis enabled the analysis of the correlation between PXRD patterns and IR spectra.

Introduction of Air-Segmentation Approach to Flow Titration by Feedback-based and Subsequent Fixed Triangular Wave-controlled Flow Ratiometry.

An air-segmentation approach has been introduced to a feedback-based and subsequent fixed triangular wave-controlled flow ratiometry to suppress axial dispersion in flow titration. The flow rate of a base solution containing an indicator is linearly varied with a control signal, Vc, supplied by a computer. The solution is merged with an acid solution under a constant total flow rate. Air is introduced to the merged solution in order to segment the solution with air bubbles. Both phases are led to a UV/Vis detector without phase separation. Air signals are removed by signal processing. The effect of the lag time between the merging of solutions upstream and the sensing of the corresponding signal downstream is offset by feedback-based upward and downward Vc scans, and thus the Vc that gives the equivalence composition is determined. Subsequently, fixed triangular wave control is applied to a narrower Vc range with a higher scan rate to enhance the throughput rate (maximally 11.8 titrations/min). Air-segmentation has been found to be effective to reduce axial dispersion and to preserve the titrand/titrant composition upon their just being merged. Consequently, the applicable range is extended especially to lower titrand concentration. The proposed method has been successfully applied to various acid-base titrations, including the nonaqueous titration of the Japanese Pharmacopoeia drug.

Bilayer Tablet Dissolution Kinetics Based on a Degassing Cyclic Flow UV-Vis Spectroscopy with Chemometrics.

Dissolution kinetics of a bilayer direct compress tablet was evaluated by using degassing cyclic flow UV-visible (Vis) spectroscopy with chemometrics. The model bilayer nicotinamide (NA)-pyridoxine hydrochloride (PH) 100.0 mg tablets were prepared via the dual compress method. The fast diffusion layer of the bilayer tablet contained nicotinamide, microcrystal cellulose, beta-lactose, magnesium stearate, and croscarmellose sodium. The slow release layer contained pyridoxine hydrochloride and carnauba wax. The monolayer direct compress tablets were prepared as dual ingredient (API)s formulation tablets. The degassing cyclic flow UV-Vis spectroscopy dissolution test was carried out using the prepared tablets. The dissolution test conditions were as follows: time, 60 min; temperature, 37°C; paddle method, 50 rpm, and UV-Vis spectra measurement 1 time/min. The UV-Vis spectra of the flow solution were measured in the range of 240-380 nm. API concentration was predicted by partial least squares (PLS) regression models based on UV-Vis spectra. The dissolution kinetics of the bilayer and monolayer tablets were evaluated based on the UV-Vis spectra with the predicted API concentration profile. The degassing flow system could prevent air bubbles in the flow cell at 1800 min. Therefore, simultaneous determination of NA and PH concentration based on the PLS regression was suggested to have high accuracy. PLS regression has advantages over the conventional λmax absorbance method of simultaneous determination. We found that the kinetics of the separated bilayer tablet can be evaluated by the same kinetic analysis method used for the single layer model tablet.

Internal Standard-Amplitude Modulated Multiplexed Flow Analysis.

A new concept of flow analysis, internal standard-amplitude modulated multiplexed flow analysis, is proposed. A proof of concept was verified by applying it to the determination of ferrous ion (Fe2+) by 1,10-phenanthroline (o-Phen) spectrophotometry. The flow rates of sample solutions containing Methylene Blue (MB) as an internal standard substance were sinusoidally varied at different frequencies. The solutions were merged with a color reagent (o-Phen) solution, while the total flow rate was held constant. Downstream, analytical signals were monitored at the maximum absorption wavelengths of Fe2+-o-Phen complex and of MB (510 and 644 nm, respectively). The signals were respectively analyzed by fast Fourier transform. The concentrations of the analytes in respective samples were simultaneously determined from the amplitudes of the corresponding wave components. The precision, linearity of the calibration curve, limit of detection and robustness against deliberate fluctuation in flow rate were greatly improved by introducing the internal standard method. Good recoveries of around 100% were obtained for Fe2+ spiked into real water samples.

Dry Mechanochemical Synthesis of Caffeine/Oxalic Acid Cocrystals and Their Evaluation by Powder X-Ray Diffraction and Chemometrics.

We report the effects of dry mechanochemical synthesis conditions on the crystallization of caffeine (CA) and oxalic acid (OX) 2:1 cocrystal. CA anhydrate and OX dihydrate were grinded at various temperatures, rotation speeds, and grinding time. The cocrystal was also synthesized by an organic solvent evaporation method, as a reference. The produced samples were measured by a powder X-ray diffraction (PXRD) analysis. The PXRD spectra suggest that the grinded cocrystal has a lower crystallinity than the evaporated one. The diffractograms for the cocrystals synthesized by 2 kinds of methods were further evaluated by multivariate curve resolution-alternating least squares method. Sources of the mathematical models constructed were assigned to the cocrystal and unreacted mixture of CA and OX dihydrate. The present approach is concluded to be useful for the improvement of pharmaceutical property because cocrystallization is closely relating to the solubility characteristics, bioavailability, stability, and so on of drugs.

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics.

We propose an approach for the simultaneous determination of multiple components in pharmaceutical mixed powder based on powder X-ray diffraction (PXRD) method coupled with chemometrics. Caffeine anhydrate, acetaminophen and lactose monohydrate were mixed at various ratios. The samples were analyzed by PXRD method in the ranges of 2θ=5.00-30.0 and 35.0-45.0 degrees. Obtained diffractograms were analyzed by conventional peak intensity method, multi curve resolution (MCR)-alternating least squares (ALS) method and partial least squares (PLS) method. Constructed PLS models can most accurately predict the concentrations among different methods used. Each regression vector of PLS correlates not only to the compound of interest but also to the coexisting compounds. The combination of PXRD and PLS methods is concluded to be powerful approach for analyzing multi components in pharmaceutical formulations.

Predictive evaluation of pharmaceutical properties of direct compression tablets containing theophylline anhydrate during storage at high humidity by near-infrared spectroscopy.

BACKGROUND: Theophylline anhydrate (TA) in tablet formulation is transformed into monohydrate (TH) at high humidity and the phase transformation affected dissolution behavior. OBJECTIVE: Near-infrared spectroscopic (NIR) method is applied to predict the change of pharmaceutical properties of TA tablets during storage at high humidity. METHODS: The tablet formulation containing TA, lactose, crystalline cellulose and magnesium stearate was compressed at 4.8 kN. Pharmaceutical properties of TA tables were measured by NIR, X-ray diffraction analysis, dissolution test and tablet hardness. RESULTS: TA tablet was almost 100% transformed into TH after 24 hours at RH 96%. The pharmaceutical properties of TA tablets, such as tablet hardness, 20 min dissolution amount (D20) and increase of tablet weight (TW), changed with the degree of hydration. Calibration models for TW, tablet hardness and D20 to predict the pharmaceutical properties at high-humidity conditions were developed on the basis of the NIR spectra by partial least squares regression analysis. The relationships between predicted and actual measured values for TW, tablet hardness and D20 had straight lines, respectively. CONCLUSIONS: From the results of NIR-chemometrics, it was confirmed that these predicted models had high accuracy to monitor the tablet properties during storage at high humidity.

Air segmented amplitude modulated multiplexed flow analysis with software-based phase recognition: determination of phosphate ion.

Amplitude modulated multiplexed flow analysis (AMMFA) has been improved by introducing air segmentation and software-based phase recognition. Sample solutions, the flow rates of which are respectively varied at different frequencies, are merged. Air is introduced to the merged liquid stream in order to limit the dispersion of analytes within each liquid segment separated by air bubbles. The stream is led to a detector with no physical deaeration. Air signals are distinguished from liquid signals through the analysis of detector output signals, and are suppressed down to the level of liquid signals. Resulting signals are smoothed based on moving average computation. Thus processed signals are analyzed by fast Fourier transform. The analytes in the samples are respectively determined from the amplitudes of the corresponding wave components obtained. The developed system has been applied to the simultaneous determinations of phosphate ions in water samples by a Malachite Green method. The linearity of the analytical curve (0.0-31.0 µmol dm(-3)) is good (r(2)>0.999) and the detection limit (3.3 σ) at the modulation period of 30s is 0.52 µmol dm(-3). Good recoveries around 100% have been obtained for phosphate ions spiked into real water samples.

Atmospheric acid gases in Tokushima, Japan, monitored with parallel plate wet denuder coupled ion chromatograph.

During the summer of 2011 and winter of 2012, we continuously measured trace acid gas concentrations in Tokushima, Japan, using a parallel plate wet denuder coupled ion chromatograph. The average concentrations of hydrochloric acid (HCl), nitrous acid (HONO), nitric acid (HNO(3)), and sulfur dioxide (SO(2)) were, respectively, 0.54, 1.20, 1.17, and 3.22 µg m(-3) in the summer, and 0.09, 1.06, 0.46, and 5.11 µg m(-3) in the winter. In the summer, concentrations of all the acid gases increased after sunrise and showed a strong diurnal pattern with daytime maxima and nighttime minima, but the time at which concentration levels began to increase and the pace of increase differed among the acid gases. The concentration of HONO increased sharply immediately after sunrise, while concentrations of the other three gases began increasing about one and half hours later. SO(2) showed the fastest rate of increase, followed by HNO(3) and HCl. These differences were likely attributable to the formation processes of gaseous substances.

On-line measurement of perchlorate in atmospheric aerosol based on ion chromatograph coupled with particle collector and post-column concentrator.

An automated analysis system has been developed for measuring perchlorate concentration in atmospheric aerosol. The perchlorate in aerosol sample, which has been collected with water mist in a hydrophobic filter/mist chamber based particle collector, is continuously preconcentrated. The matrix ions such as sulfate are subsequently removed from the preconcentrator. The remaining perchlorate is then analyzed on-line with an ion chromatograph in conjunction with a Nafion membrane tube based post-column concentrator. The sensitivity is increased by a factor of 7.7 with the post-column concentration technique. The proposed system has been successfully operated at Tokushima, Japan. The limit of detection is 0.35 ng/m(3) for 3 h sampling cycle. The perchlorate concentration in the atmospheric aerosol averaged 1.01±1.75 ng/m(3) (n=12).

Simultaneous determination of nitrite and nitrate ions by air-segmented amplitude-modulated multiplexed flow analysis.

The concept of amplitude-modulated multiplexed flow analysis has been extended to the simultaneous determination of multiple analytes in a sample. A sample solution containing nitrite and nitrate ions is delivered from two channels, but the flow rates are varied at different frequencies. One of the channels has a reduction column for converting nitrate ions to nitrite ions. Downstream, the absorbance of the diazo-coupling product is monitored after the merging of both solutions with a Griess reagent. The signal is analyzed by a fast Fourier transform (FFT) in real time. From the thus-obtained amplitude, a µmol dm(-3) level of the ions can be determined. The introduction of air bubbles is effective to reduce any axial dispersion, and hence to improve the sensitivity.

Parallel-plate wet denuder coupled ion chromatograph for near-real-time detection of trace acidic gases in clean room air.

This paper describes the performance of our automated acidic (CH(3)COOH, HCOOH, HCl, HNO(2), SO(2), and HNO(3)) gases monitor utilizing a parallel-plate wet denuder (PPWD). The PPWD quantitatively collects gaseous contaminants at a high sample flow rate (∼8 dm(3) min(-1)) compared to the conventional methods used in a clean room. Rapid response to any variability in the sample concentration enables near-real-time monitoring. In the developed monitor, the analyte collected with the PPWD is pumped into one of two preconcentration columns for 15 min, and determined by means of ion chromatography. While one preconcentration column is used for chromatographic separation, the other is used for loading the sample solution. The system allows continuous monitoring of the common acidic gases in an advanced semiconductor manufacturing clean room.

Air-segmented amplitude-modulated multiplexed flow analysis.

Air-segmentation is applied to amplitude-modulated multiplexed flow analysis, which we proposed recently. Sample solutions, the flow rates of which are varied periodically, are merged with reagent and/or diluent solution. The merged stream is segmented by air-bubbles and, downstream, its absorbance is measured after deaeration. The analytes in the samples are quantified from the amplitudes of the respective wave components in the absorbance. The proposed method is applied to the determinations of a food dye, phosphate ions and nitrite ions. The air-segmentation is effective for limiting amplitude damping through the axial dispersion, resulting in an improvement in sensitivity. This effect is more pronounced at shorter control periods and longer flow path lengths.

Analytical parameters for amplitude-modulated multiplexed flow analysis.

Analytical conditions of amplitude-modulated multiplexed flow analysis, the basic concept of which was recently proposed by our group, are investigated for higher sample throughput rate. The performance of the improved system is evaluated by applying it to the determination of chloride ions. The flow rates of two sample solutions are independently varied in accordance with sinusoidal voltage signals, each having different frequency. The solutions are merged with a reagent solution and/or a diluent, while the total flow rate is held constant. Downstream, the analytical signal V(d) is monitored with a spectrophotometer. The V(d) shows a complicated profile resulting from amplitude modulated and multiplexed information on the two samples. The V(d) can, however, be deconvoluted to the contribution of each sample through fast Fourier transform (FFT). The amplitudes of the separated wave components are closely related to the concentrations of the analytes in the samples. By moving the window for FFT analysis with time, a temporal profile of the amplitudes can be obtained in real-time. Analytical conditions such as modulation period and system configuration have been optimized using aqueous solutions of Malachite Green (MG). Adequate amplitudes are obtained at the period of as low as 5 s. At this period, the calibration curve for the MG concentration of 0-30 micromol dm(-3) has enough linearity (r(2) = 0.999) and the limit of detection (3.3sigma) is 1.3 micromol dm(-3); the relative standard deviation of repeated measurements (C(MG) = 15 micromol dm(-3), n = 10) is 2.4%. The developed system has been applied to the determination of chloride ions by a mercury(II) thiocyanate method. The system can adequately follow the changes in analyte concentration. The recoveries of chloride ion spiked in real water samples (river and tap water) are satisfactory, around 100%.

Spectrophotometric determination of trace phosphate ions by amplitude-modulated flow analysis coupled with malachite green method.

An amplitude-modulated flow analysis coupled with lock-in detection is proposed for the determination of trace phosphate. The flow rate F(S) of sample solution is varied in response to a periodic signal V(c) of alternating waveform. A coloring reagent solution (ammonium molybdate + Malachite Green) is delivered at a constant flow rate F(R). Under the constant total flow rate F(T), both solutions are merged with a diluent (water). Phosphate ion in the sample reacts with molybdate and then with Malachite Green to form green ion pairs in acidic media. Downstream, the absorbance of the mixed solution is measured at 625 nm. The output voltage V(d) from the detector is sent to a lock-in amplifier, where the wave component of V(d) that has the same frequency as that of V(c) is distinguished from background signals. Phosphate ion can be determined from the amplitude of the component thus extracted. The calibration curve is linear (r(2) > 0.998) and the limit of detection (3.3sigma) is 0.17 micromol dm(-3). Compared with a conventional flow-based method with no modulation, the present method is less susceptible to the baseline drift due mainly to the adsorption of the ion-pair on the optical window, because the quantification is based not on the absorbance itself but on the amplitude of the absorbance. Good recoveries around 100% are obtained for the phosphate ions spiked into real water samples.