Development and validation of a near-infrared method for the quantitation of caffeine in intact single tablets

A near-infrared spectroscopic method was developed and validated for determining the caffeine concentration of single and intact tablets in a Finnish pharmaceutical product containing 58.82% (m/m) caffeine.The spectral region of interest contained a total of 474 data points. The second derivative of Savitsky-Golay, a standard normal variate, and mean centering were used as spectral preprocessing options. The feasibility study showed nonuniformity of caffeine repartition within each tablet. Thus, spectra were recorded from both faces of the tablets, and the analysis result for a single tablet was reported as the average of both face determinations. Precision of the method was validated because the relative standard deviations from repeatability and intermediate precision tests were below 0.75% (m/m). Accuracy validation proved that the NIR results were not significantly different (P = 0.09, n = 12) from the results obtained with the reference HPLC method. The limit of quantification for caffeine was 13.7% (m/m) in the tablets. The method was found to be unaffected by NIR source replacement, but the repeatability of the results was affected if the sample holder was not placed in the correct position in the light beam. Routine NIR analysis of caffeine in tablet form was found to be more flexible and much faster than that performed with the HPLC method.     

A comparative study of recent relay autotuning methods for multivariable systems

A typical procedure for designing multivariable controllers is the following: build a model for the multivariable process, choose the control structure, calculate the control parameters, test the controller (possibly with simulation) and then retune controller parameters as necessary. This procedure is complex and time consuming even for scalar control loops. For multivariable controllers, the procedure is even more daunting. Automation of the design method is and has been a concern of many researchers. There has been a large number of papers on relay autotuning of control systems. The choice of relay feedback to solve the design problem is justified by the possible integration of system identification and control into the same design strategy, giving birth to relay autotuning. In this paper, nine different relay autotuning methods for multivariable systems are compared. Most of these methods have common basics but they may differ in the tuning procedure, convergence, identification method, control structure and performance achievement. The paper summarizes these methods and investigates the advantages and drawback of each algorithm.     

Performance evaluation of an automation system — determination of a benchmzrk process

An average “real” process is determined from 55 processes automated by an automation system. This a first step in developing realistic benchmark processes for making objective evaluation tests between the performance of different automation systems. The most important properties of the average process that are independent of the automation system used and that are important performance indicators are presented in the paper.The real process, representing the statistical mean of the process data best, is a papermachine with a pulp making department. The process has 141 analog inputs, 50 binary inputs, 90 analog outputs, 63 binary outputs, 77 motor controls, 8 motor value controls, 308 process interfaces, and 165 displays.     

3‐Heterocycle‐Phenyl N‐Alkylcarbamates as FAAH Inhibitors: Design,Synthesis and 3D‐QSAR Studies

Carbamates are a well‐established class of fatty acid amide hydrolase (FAAH) inhibitors. Here we describe the synthesis of meta‐substituted phenolic N‐alkyl/aryl carbamates and their in vitro FAAH inhibitory activities. The most potent compound, 3‐(oxazol‐2yl)phenyl cyclohexylcarbamate ( 2 a ), inhibited FAAH with a sub‐nanomolar IC₅₀ value (IC₅₀=0.74 nM ). Additionally, we developed and validated three‐dimensional quantitative structure–activity relationships (QSAR) models of FAAH inhibition combining the newly disclosed carbamates with our previously published inhibitors to give a total set of 99 compounds. Prior to 3D‐QSAR modeling, the degree of correlation between FAAH inhibition and in silico reactivity was also established. Both 3D‐QSAR methods used, CoMSIA and GRID/GOLPE, produced statistically significant models with coefficient of correlation for external prediction (R²_PRED) values of 0.732 and 0.760, respectively. These models could be of high value in further FAAH inhibitor design.     

Biological effects of casein-derived tripeptide powders are not affected by fermentation process

Milk casein-derived biologically active tripeptides isoleucine–proline–proline and valine–proline–proline have shown antihypertensive effects both in animal and clinical studies. Contradictory findings from clinical intervention studies may be related to different manufacturing processes. The present study aimed to compare cardiovascular effects of two different tripeptide powders in spontaneously hypertensive rat (SHR). Rats received tripeptide powders produced either by Lactobacillus helveticus fermentation (A) or Lb. helveticus plus proline specific endoprotease (B) in drinking fluid for 8 weeks. Systolic blood pressure was recorded weekly. At the end, blood and tissue samples were collected and arterial responses studied. Blood pressure was 13.6 and 14.2 mmHg lower in the groups A and B, respectively, versus the water group (P < 0.01). Vascular responses of aorta and mesenteric artery did not differ between the groups. Both tripeptide products increased urinary cGMP (P < 0.001) and decreased albumin (P < 0.05). The fermentation process did not influence the cardiovascular effects of the tripeptide powders.     

Development of color density concept with color difference formulas in respect to human vision system

The aims of this study are to develop the color density concept and to propose the color density based color difference formulas. The color density is defined using the metric coefficients that are based on the discrimination ellipses and the locations of the colors in the color space. The ellipse sets are the MacAdam ellipses in the CIE 1931 xy-chromaticity diagram and the chromaticity-discrimination ellipses in the CIELAB space. The latter set was originally used to develop the CIEDE2000 color difference formula. The color difference can be calculated from the color density for the two colors under consideration. As a result, the color density represents the perceived color difference more accurately, and it could be used to characterize a color by a quantity attribute matching better to the perceived color difference from this color. Resulting from this, the color density concept provides simply a correction term for the estimation of the color differences. In the experiments, the line element formula and the CIEDE2000 color difference formula performed better than the color density based difference measures. The reason behind this is in the current modeling of the color density concept. The discrimination ellipses are typically described with three-dimensional data consisting of two axes, the major and the minor, and the inclination angle. The proposed color density is only a one-dimensional corrector for color differences; thus, it cannot capture all the details of the ellipse information. Still, the color density gives clearly more correct estimations to perceived color differences than Euclidean distances using directly the coordinates of the color space.     

Poly(vinyl pyrrolidone)—C70 complexes in aqueous solutions

Aqueous solutions of poly(vinyl pyrrolidone)-fullerene complexes (PVP-C₇₀) have been studied using static and dynamic light scattering methods. Two diffusive processes were detected. The slow diffusion was interpreted as dynamics of large intermolecular PVP-C₇₀ complexes while the fast diffusion was associated with the presence of individual PVP molecules in solution. It was also shown that the molecular weights and dimensions of PVP-C₇₀ complexes are smaller than for PVP-C₆₀ by a factor of 2.5-3. In aqueous solutions of PVP-C₇₀ complex the depolarization and dissymmetry of scattered light were observed in contrast to PVP-C₆₀ solutions. It reveals the existence of anisotropic structures in PVP-C₇₀ solutions. Intermolecular interactions within PVP-C₇₀ complexes are weak and a hydrodynamic field can destroy complexes.     

The initial stages of multicomponent particle formation during the gas phase combustion synthesis of mixed SiO2/TiO2

The ability to properly scale the synthesis of advanced materials through combustion synthesis routes is limited by our lack of knowledge regarding the initial stages of particle formation. In flame aerosol reactors, the high temperatures, fast reaction rates, and flame chemistry can all play a critical role in determining the properties of the resulting nanomaterials. In particular, multicomponent systems pose a unique challenge as most studies rely on empirical approaches toward designing advanced composite materials. The lack of predictive capabilities can be attributed to a lack of data on particle inception and growth below 2 nm. Measurements for the initial stages of particle formation during the combustion synthesis of SiO₂ and composite SiO₂/TiO₂ using an atmospheric pressure inlet time-of-flight mass spectrometer are presented. Both positively and negatively charged clusters can be measured and results show the presence of silicic acid species which grow through dehydration, hydrogen abstraction, and interactions with hydroxyl radicals. In the case of composite SiO₂/TiO₂ particle formation, new molecular species containing Ti atoms emerge. Tandem differential mobility analysis-mass spectrometry (DMA-MS) provided further insight into the size-resolved chemistry of particle formation to reveal that at each cluster size, further hydroxyl-driven reactions take place. From this we can conclude that previous assumptions on collisional growth from simple monomer species of SiO₂ and TiO₂ do not sufficiently describe the collisional growth mechanisms for particle growth below 2 nm.

Copyright © 2018 American Association for Aerosol Research     

Analysis of regioisomers of triacylglycerols of northern currant seed oil by tandem mass spectrometry

Currant oils have special health properties due to their moderate contents of α‐linolenic, γ‐linolenic and stearidonic acids. The distribution of fatty acids (FA) in the triacylglycerols (TAG) may affect the beneficial effects. Seed oils of wild northern red currant (NRC) (Ribes spicatum L.) from Northern Finland and of wild alpine currant (AC) (R. alpinum L.) from the South‐West coast of Finland were investigated. The purified TAG were analysed by tandem mass spectrometry by applying the ammonia negative ion chemical ionisation – collision‐induced dissociation method. Molecular weight fractions rich in C18:3 FA and C18:4 FA were investigated. Of the total oil, the molecular weight species 54:7 (ACN:DB), 54:8 and 54:9 were more abundant in NRC than in AC, being 21.0%, 15.8%, 7.4% and 16.2%, 11.2%, 4.8%, respectively (p <0.05). The species 52:6 was more abundant in AC (3.1%) than in NRC (2.6%) (p <0.05). The preferential order of FA to be in the sn‐2 position in both berries was typically C18:1 > C18:2 > C18:4 > C18:3. No difference was observed between relative locations of C16:0 FA and C18:3 FA in either of the oils. Within the TAG consisting of FA combinations C18:3/C18:3/C18:1 (54:7), C18:1 was more preferentially in the sn‐2 position (p <0.05) in AC (93.2%) than in NRC (74.6%), and in the case of C18:3, the preference was vice versa. Within the molecular weight species 54:9, FA combination C18:4/C18:3/C18:2, linoleic acid preferentially occupied the secondary position (p <0.005) in both berries, and the proportion of the TAG regioisomer pair sn‐C18:3‐C18:4‐C18:2 + sn‐C18:2‐C18:4‐C18:3 was more abundant (30.2%) in NRC than in AC (15.3%). Within the TAG species 52:6, proportions of all the existing combinations, C16:0/C18:3/C18:3, C16:0/C18:4/C18:2 and C16:1/C18:3/C18:2, varied between the two berry species (p <0.005).     

Liquid Chromatography–Light Scattering Detector–Mass Spectrometric Analysis of Digested Oxidized Rapeseed Oil

Rapeseed oil was oxidized chemically and thermally to produce two distinct oxidized oils. These oils, along with unoxidized oils, were subjected to an artificial digestion model to simulate the digestive processes in humans. Lipid digestion involves lipases that break down the intact triacylglycerol (TAG) molecules first to diacylglycerols, and eventually to sn-2-monoacylglycerols (MAG) and free fatty acids. A high performance liquid chromatography-evaporative light scattering detector-electrospray ionization-mass spectrometric (HPLC–ELSD–ESI–MS) method was developed to monitor the lipolysis and the presence of oxidized lipids. The HPLC–ELSD–ESI–MS analysis enabled the separation and detection of nearly all the lipid species present in the sample after TAG hydrolysis. The HPLC–MS analyses of digestion products revealed that oxidized triacylglycerols are hydrolyzed by the digestive enzymes in a manner similar to that of native, unoxidized molecules. Significant amounts of sn-1(3)-MAG were found in all the samples after lipolysis, however, more of these were found in unoxidized rapeseed oil samples than in the oxidized oils. Several oxidized molecules were identified with the aid of synthesized oxylipids. This novel method is scalable to small-scale preparative fractionation of oxidized lipid molecules from a complex digestion sample. Also, the fingerprint-like, diagnostic, MS profiles of oxidized oils, reference compounds, and digestion products may be a great aid in comprehensive analysis of lipid oxidation and lipolysis.