- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: The effect of hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) on carbamazepine (CBZ) polymorphic transformation has been investigated by an attenuated total reflectance-infrared (ATR-IR) spectroscopy and chemoinformatics. CBZ anhydrate samples were each kneaded with 35.0 μL of pure water, aqueous solution of 0.005 w/v% HPC, or that of 0.005 w/v% HPMC. Each paste was put on a germanium glass of an ATR accessory and was covered with a sheet of Parafilm® at 20 ± 2 °C. Measured IR spectra were analyzed by a multivariate curve resolution-alternating least squares (MCR-ALS) and a two-dimensional correlation spectroscopic analysis. Source vectors of MCR-ALS were assigned to CBZ anhydrate and dihydrate. Concentration data of MCR-ALS were evaluated for the kinetics of CBZ polymorphic transformation. The combination of ATR-IR spectroscopy and MCR-ALS is concluded to be useful for the elucidation of rapid polymorphic transformation in suspension. The transformation rate is delayed by HPC and HPMC.
- [Show abstract] [Hide abstract] ABSTRACT: Rapid self-setting apatite cement (SSAC) formation from tetracalcium phosphate (TeCP) and dicalcium phosphate dihydrate (DCPD) has been investigated by an attenuated total reflection Fourier transform infrared (ATR-IR) spec-troscopy coupled with a principal component analysis (PCA). After TeCP and DCPD were kneaded with phosphoric acid, the peaks of ATR-IR spectra for the kneaded sample shift significantly in the ranges of 2250–2400 and 850– 1150 cm −1 due to the crystalline transformation into hydroxy-apatite (HAp). The PCA results indicate that the loadings of principal components 1 and 2 (PC1 and PC2, respectively) are ascribed to CO 2 and phosphate group, respectively, in the transforming cement. The PC1 score initially increases to reach a maximum at around 1000 s and then decreases. In contrast, the PC2 score increases continuously, but its increment became lesser with time. Although the profiles of PC2 score against PC1 score are similar in shape, there are deviations among the profiles obtained through quadruplicate experiments. The scores are, therefore, time differentiated, and the relationship between the differentiated scores is analyzed. The time differentiation approach is found to be useful for understanding complicated chemical reactions. The PCA results suggest that SSAC formation can be divided into three major stages. In the first stage, CO 2 concentration in the transforming cement rapidly increases, which triggers HAp crystallization. In the second stage, CO 2 concentration still increases, but its increasing rate drastically decreases; HAp crystallization continues with increasing rate. In the last stage, CO 2 concentration decreases, and HAp crystallization significantly slows down.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: A fast and simple pretreatment method of phosphorus compounds using Co3+ has been studied for the spectrophotometric determination of total phosphorus in water samples. Sample was mixed with a pretreatment solution (0.05 mol dm-3 CoSO4 in 1 mol dm-3 H2SO4) in an electrolytic cell at the volume ratio of 4:1. Highly reactive Co3+ was continuously generated through the electrolysis of Co2+ during the pretreatment. Aliquot of the solution was injected to the system of flow injection - Molybdenum Blue spectrophotometry in order to evaluate phosphate ion (PO43-) produced. Organic phosphorus compounds are completely decomposed to PO43- within 2 min by Co3+ under moderate condition (70°C). The Co3+ is also effective for the acid hydrolysis of polyphosphates; diphosphate and tripolyphosphate are converted to PO43- within 8 min through the pretreatment. Possible mechanisms of the pretreatment are discussed based on the strong oxidizing activity and the Lewis acid nature of Co3+.
- [Show abstract] [Hide abstract] ABSTRACT: 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 (0.0-31.0μmoldm(-3)) is good (r(2)>0.999) and the detection limit (3.3σ) at the modulation period of 30s is 0.52μmoldm(-3). Good recoveries around 100% have been obtained for phosphate ions spiked into real water samples.
- [Show abstract] [Hide abstract] ABSTRACT: An annular wet denuder with both annular surfaces functioning as a sink for gaseous molecules is described. A gas absorbing solution was continuously flowed down the stainless-steel inner tube exterior and the outer tube interior gas collection surfaces of the denuder. In order to enhance the gas collection efficiency, the gas collection surfaces were modified with a Nylon monofilament and a perfluoroalkoxy alkane screen mesh cloth. The collection efficiency was increased by coiling the monofilament around the inner tube exterior, and by fixing the screen mesh cloth on the outer tube interior (e.g. 1.67 ± 0.06 and 1.77 ± 0.01 times at a gas absorbing solution flow rate of 0.30 cm3 min−1 tube−1, respectively). At a sampling flow rate of 1.0 dm3 min−1, 97.7 ± 0.53% of the trace gas was collected with the surface modified annular wet denuder. The response speeds of the analytical signal change (10% → 90% and 90% → 10%) were 5.0 ± 0.9 min and 4.4 ± 0.2 min, respectively. Quantitative collection of water-soluble trace gas and reasonably rapid response time were achieved with the developed device.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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).
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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.
- [Show abstract] [Hide abstract] ABSTRACT: 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%.
- [Show abstract] [Hide abstract] ABSTRACT: We propose a new concept, amplitude modulated multiplexed flow analysis, for the simultaneous determination of multiple analytes from a single continuous analytical signal. The flow rates (FS1 and FS2) of two sample solutions are independently varied in response to trigonometric voltage signals each at a different anharmonic frequency. With the total flow rate FT held constant, the solutions are merged with a reagent solution that is aspirated to the confluence point at the flow rate of FT−FS1−FS2. Downstream, the analytical signal due to the mixed reacted solution, Vd, is monitored. Vd will show a complicated profile resulting from the trigonometrically varying flow rates of the sample solutions. The signal contains information on the multiple analytes. The signal can be demodulated to the contribution of each sample solution through fast Fourier transform (FFT). The amplitudes of the separated wave components are related to the concentration of the analytes in the sample solutions. By moving a window for FFT analysis with time, temporal profile of amplitudes can be obtained in real-time. We demonstrate the concept by applying it to the simultaneous determination of food dyes and to that of ferrous ions in two sample solutions.
- [Show abstract] [Hide abstract] ABSTRACT: We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18), for the determination of the lipophilicity of drugs with diverse chemical nature ranging from acidic to basic. A set of 40 model compounds with well-defined solvatochromic parameters was selected to allow a broad distribution of structural properties. The chromatographic results showed that the lipophilicity index log k(w) obtained with XBridge Shield RP(18) was well correlated with experimental log P(oct) values (r(2)=0.96). Linear solvation free-energy relationship (LSER) analyses revealed that the retention mechanism of the stationary phase and 1-octanol/water partitioning were controlled by almost the same balance of intermolecular forces (hydrophobicity as expressed by the van der Waals volume V(w), H-bond acceptor basicity beta, and dipolarity/polarizability pi*). The results showed that XBridge Shield RP(18) phase overcomes the shortcomings of the silica-based stationary phases, the application of which to lipophilicity measurements had been limited to neutral and acidic compounds.
- [Show abstract] [Hide abstract] ABSTRACT: We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica-based stationary phase, XBridgel (TM) Shield RP18, for the determination of the lipophilicity of drugs with diverse chemical nature ranging from acidic to basic. A set of 40 model compounds with well-defined solvatochromic parameters was selected to allow a broad distribution of structural properties. The chromatographic results showed that the lipophilicity index logk(w) obtained with XBridge (TM) Shield RP18 was well correlated with experimental logP(oct) values (r(2) =0.96). Linear solvation free-energy relationship (LSER) analyses revealed that lite retention mechanism of the stationary phase and 1-octanol/water partitioning were controlled by almost the same balance of intermolecular forces (hydrophobicity as expressed by the van der Waals volume V-w,V- H-bond acceptor basicity beta, and dipolarity/polarizability pi*). The results showed that XBridge (TM) Shield RP18 phase overcomes the shortcomings of the silica-based stationary phases, the application of which to lipophilicity measurements had been limited to neutral and acidic compounds.
- [Show abstract] [Hide abstract] ABSTRACT: Lipophilicity was evaluated using a novel RP-HPLC stationary phase (Discovery-RP-Amide-C16) with and without 1-octanol added to the mobile phase. A set of 46 drugs and flavonoids characterized by a broad structural diversity and a wide log Poct range (-0.69 to 5.70) was selected for this study. This set consists of neutral solutes and solutes with acidic or ampholytic functionalities which were maintained neutral at pH 2.5 or 4. In our conditions, the addition of 1-octanol in the mobile phase proved a key factor to derive a lipophilicity index log k(w) highly correlated with log Poct for all investigated solutes. 1-Octanol improved the correlation between log Poct and log k(w) mainly by influencing the retention behavior of the solutes with log Poct values below +3. This study brings additional evidence that under proper experimental conditions of stationary and mobile phases, RP-HPLC is a very useful method to obtain log Poct values.
- [Show abstract] [Hide abstract] ABSTRACT: We propose a new approach for high-throughput continuous titration based on a flow ratiometry. The method was applied to potentiometric titrations of acids and bases. A base solution, the flow rate F(B) of which was varied in response to controller output voltage V(c), was merged with an acid solution under constant total (acid+base) flow rate. Downstream, the pH of the mixed solution was measured with a flow-through glass electrode. Initially, V(c), and thus F(B) was increased linearly. At the instant the equivalence point (EP) was sensed, the ramp direction of V(c) was reversed from upward to downward. The direction was reversed to upward when EP was sensed again. Such the feedback-based operation gives a triangular waveform of V(c), because there is a delay corresponding mainly to the transit time of merged solutions to reach the sensor. The value of V(c) that gives EP composition, V(E), was estimated by averaging the most recent maximum and minimum values of V(c). Next, fixed triangular waves of V(c) was used to control F(B). The amplitude and the scan rate of the waves were fixed narrower and faster, respectively, than those in the feedback-based operation in order to improve the throughput rate. The EP can be located as long as the scan range covers V(E). These automated processes limited the titration to just the narrow range around EP, and thus realized extremely high throughput rate of maximally 17.6 titrations per minute (=3.4s per titration) at R.S.D.=0.35%.
- [Show abstract] [Hide abstract] ABSTRACT: The principle of flow ratiometry for high-throughput titration, which we recently proposed for potentiometric titration, was extended to photometric titration. The flow rate (FB) of a base solution containing an acid-base indicator was linearly varied in response to a control voltage (Vc) generated from a computer. With the total (acid + base) flow rate (FT) being kept constant, the base solution was merged with an acid solution, which was aspirated to the confluence point at a flow rate of FT - FB. Downstream, the relative transmittance of the mixed solution was measured at the maximum absorption wavelength of the base form of the indicator. Initially, a feedback-based control was applied, where the scan direction of Vc was reversed from upward to downward, and vice versa, whenever the transition of the indicator at the equivalence point (EP) was sensed. Next, the scan range of V. was further limited to the range just around EP by using fixed triangular waves. These processes avoided scanning in a range of no interest. Thus, an unprecedentedly high throughput rate (maximally 34 titrations per minute, corresponding to 1.76 s per titration) was realized with reasonable precision (RSD < 0.5%).
The University of Tokushima
Tokusima, Tokushima, Japan
- • Institute of Health Biosciences (HBS)
- • Faculty of Pharmaceutical Sciences