A Wet Gas Metering System Based on the Extended-Throat Venturi Tube.

Although the use of a classical Venturi tube for wet gas metering has been extensively studied in the literature, the use of an extended-throat Venturi (ETV) tube has rarely been reported since its first proposal by J. R. Fincke in 1999. The structure of an ETV is very simple, but due to the complexity of multiphase flow, its theoretical model has not been fully established yet. Therefore, in this paper theoretical models have been developed for the convergent and throat sections of an ETV, and the gradients of front and rear differential pressures are derived analytically. Several flowrate algorithms have been proposed and compared with the existing ones. Among them, the iteration algorithm is found to be the best. A reasonable explanation is provided for its performance. The relationship between the differential pressure gradient and the flowrate relative error is also studied, such that the relative error distributions varying with ETV measured flowrates can be derived. The gas flowrate error of ETV increases with the liquid content whilst the liquid flowrate error of ETV decreases with the liquid content, and the relative errors of liquid flowrate are generally 2 to 3 times larger than that of the gas flowrate. Finally, the ETV tends to be more accurate than the classical Venturi tube. The ETV can be designed more compact under the same signal intensity due to its significantly higher velocity in the throat section.

A Novel Multi-Sensor Fusion Algorithm Based on Uncertainty Analysis.

During the research and development of multiphase flowmeters, errors are often used to evaluate the advantages and disadvantages of different devices and algorithms, whilst an in-depth uncertainty analysis is seldom carried out. However, limited information is sometimes revealed from the errors, especially when the test data are scant, and this makes an in-depth comparison of different algorithms impossible. In response to this problem, three combinations of sensing methods are implemented, which are the "capacitance and cross-correlation", the "cross-correlation and differential pressure" and the "differential pressure and capacitance" respectively. The analytical expressions of the gas/liquid flowrate and the associated standard uncertainty have been derived, and Monte Carlo simulations are carried out to determine the desired probability density function. The results obtained through these two approaches are basically the same. Thereafter, the sources of uncertainty for each combination are traced and their respective variations with flowrates are analyzed. Further, the relationship between errors and uncertainty is studied, which demonstrates that the two uncertainty analysis approaches can be a powerful tool for error prediction. Finally, a novel multi-sensor fusion algorithm based on the uncertainty analysis is proposed. This algorithm can minimize the standard uncertainty over the whole flowrate range and thus reduces the measurement error.

Determination of residual 4-nitrobenzaldehyde in chloramphenicol and its pharmaceutical formulation by HPLC with UV/Vis detection after derivatization with 3-nitrophenylhydrazine.

4-Nitrobenzaldehyde is the synthetic raw material and an important photodegradation product of chloramphenicol. With a structural "alert" of human genotoxic potential and reported mutagenicity, this compound should be controlled in drug substances as a potential genotoxic impurity. However, current analysis methods require complex pre-treatment processes and/or lack sufficient specificity and sensitivity. Nitrophenylhydrazine is a common carbonyl derivatization reagent used to determine the residual aromatic aldehydes in drug samples. In the present study, we report an unexpected advantage of 3-nitrophenylhydrazine hydrochloride as a derivatization reagent in the derivatization high-performance liquid chromatography-ultraviolet detection method to determine 4-nitrobenzaldehyde in chloramphenicol samples. Compared with other nitro-substituted phenylhydrazines, 3-nitrophenylhydrazine hydrochloride can minimize drug matrix and derivatization reagent interferences, since the maximum absorption wavelength of its derivative is significantly red-shifted to 397 nm. The derivatization conditions have been optimized in terms of reaction efficiency, including reaction temperature, time, and diluting solvent, through a design of experiments. As a result, after reaction with 500 µg mL-1 of 3-nitrophenylhydrazine hydrochloride in acetonitrile-water (70:30, v/v) at 60 °C for 30 min, the developed HPLC method could be used to determine 4-nitrobenzaldehyde with a limit of detection of 0.009 µg mL-1. The method was then validated and applied for the determination of residual 4-nitrobenzaldehyde in chloramphenicol and its eye-drop samples.

Determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid by derivatization followed by high-performance liquid chromatography with ultraviolet detection.

Methanesulfonic acid is routinely used in pharmaceuticals but can contain potentially genotoxic impurities such as methyl methanesulfonate and ethyl methanesulfonate. The aim of this study was to develop a simple high-performance liquid chromatography with ultraviolet detection method for determining methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid. Samples (250 mg) in water/acetonitrile (200 µL) were first combined with 10.0 mol/L sodium hydroxide solution (270 µL). Then they were mixed with 2.0 mg/mL N,N-diethyldithiocarbamate (500 µL), diluted to 5 mL with N,N-dimethylacetamide and allowed to react at 80°C for 1 h. The derivatives were analyzed using gradient high-performance liquid chromatography with ultraviolet detection (277 nm) and structurally elucidated by liquid chromatography with mass spectrometry. With acetonitrile/5 mmol/L ammonium acetate solution as the eluent and 1 mL/min as the flow rate on a C18 column, the derivatives were eluted at 10.6 and 14.8 min. Good linearity (correlation coefficients > 0.999) and low limits of quantitation (0.6 ppm) were obtained. The recoveries were in the range of 80-115% with relative standard deviation < 5.0%. Finally, the established method was successfully used for the determination of methyl methanesulfonate and ethyl methanesulfonate in methanesulfonic acid.

Development and validation of a general derivatization HPLC method for the trace analysis of acyl chlorides in lipophilic drug substances.

Acyl chlorides are important acylating agents in the synthesis of active pharmaceutical ingredients. Determining the residual acyl chlorides in drug substances is a challenge due to their high reactivity and the matrix interferences from drug substances and their related impurities. This paper describes a general derivatization HPLC method for the determination of aromatic and aliphatic acyl chlorides in lipophilic drug substances. Since most drug substances have weak absorptions in the visible range (above 380nm), the nitro-substituted anilines and nitro-substituted phenylhydrazines were selected as the derivatization reagents due to their weak basicity and red-shift of UV absorption spectra. The maximum wavelength and absorption intensity of nitro-substituted anilines decreased after derivatization with acyl chlorides, whereas the derivatization products of nitro-substituted phenylhydrazines showed the slight increases of maximum wavelength and absorbance intensity. Hence, 2-nitrophenylhydrazine was selected as the suitable derivatization reagent because the derivatives have the maximum UV wavelength absorbance at 395nm, which could largely minimize the matrix interferences. The optimization of the concentration of 2-nitrophenylhydrazine is important for the sensitivity and stability of derivatives. Other reaction conditions including reaction temperature, time and the influence of three competitive solvents (water, methanol and ethanol) on the reaction efficiency were also studied. After derivatization with 100µgmL-1 2-nitrophenylhydrazine at room temperature for 30min, the method was validated for high specificity and sensitivity with the detection limits in the range of 0.01-0.03µgmL-1. The proposed method was applied as a generic method to determine the residual acyl chlorides in lipophilic drug substances.