Relative Standard Errors Of Prediction Research Articles

The Use of a Closed Feed Frame for the Development of Near-Infrared Spectroscopic Calibration Model to Determine Drug Concentration.

This study evaluates the use of the closed feed frame as a material sparing approach to develop near-infrared (NIR) spectroscopic calibration models for monitoring blend uniformity. The effect of shear induced by recirculation on NIR spectra was also studied. Calibration models were developed using NIR spectra obtained in the closed feed frame for two cases. For case 2, blends that flowed through the open feed frame were predicted with the model. The shear effect of the feed frame on the blends was assessed through the characterization of powder properties before and after recirculation. The physical characterization of the blends confirmed that the powder properties were not altered after recirculation within the closed feed frame. Both calibration models provided highly accurate predictions of the test sets with low bias (0.03% w/w and -0.06% w/w) and relative standard error of prediction (1.9% and 3.7%), respectively. The predictive performance of the calibration models was not affected by the shear effect. Recirculation within the closed feed frame did not change the physical properties of the blends studied. The prediction of blends flowing through the open feed frame was possible with a calibration model developed in the closed feed frame. The closed feed frame could reduce the materials needed to develop calibration models by more than 90%.

Application of MIA-QSAR in Designing New Protein P38 MAP Kinase Compounds Using a Genetic Algorithm

Multivariate image analysis quantitative structure-activity relationship (MIA-QSAR) study aims to obtain information from a descriptor set, which are image pixels of two-dimensional molecule structures. In the QSAR study of protein P38 mitogen-activated protein (MAP) kinase compounds, the genetic algorithm application for pixel selection and image processing is investigated. There is a quantitative relationship between the structure and the pIC50 based on the information obtained. (The pIC50 is the negative logarithm of the half-maximal inhibitory concentration ( IC50 ), so pIC50 = −log IC50 .) Protein P38 MAP kinase inhibitors are used in the treatment of malignant tumors. The development of a model to predict the pIC50 of these compounds was performed in this study. To accomplish this, the molecules were first plotted and fixed in the same coordinates in ChemSketch. Then, the images were processed in the MATLAB program. Partial least squares (PLS) model, orthogonal signal correction partial least squares (OSC-PLS) model, and genetic algorithm partial least squares (GA-PLS) model methods are used to generate quantitative models, and pIC50 prediction is performed. The GA-PLS model has the highest predictive power for a series of statistical parameters such as root mean square error of prediction (RMSEP) and relative standard errors of prediction (RSEP). Finally, the molecular junction (docking) was done for predicted molecules in quantitative structure activity relationship (QSAR) with an appropriate receptor and acceptable results were obtained. These results are good and proper for the prediction of compounds with better properties.

Quantitative Determination of Diosmin in Tablets by Infrared and Raman Spectroscopy

Diosmin is widely used in the treatment of chronic venous diseases and hemorrhoids. Based on Raman and infrared reflection spectra of powdered tablets in the mid- and near-infrared regions and results of reference high-performance liquid chromatographic analysis, partial least squares models that enable fast and reliable quantification of the studied active ingredient in tablets, without the need for extraction, were elaborated. Eight commercial preparations containing diosmin in the 66-92% (w/w) range were analyzed. In order to assess and compare the quality of the developed chemometric models, the relative standard errors of prediction for calibration and validation sets were calculated. We found these errors to be in the 1.0-2.4% range for the three spectroscopic techniques used. Diosmin content in the analyzed preparations was obtained with recoveries in the 99.5-100.5% range.

In-line spectroscopy combined with multivariate analysis methods for endpoint determination in column chromatographic adsorption processes for herbal medicine

Objective: In a chromatographic cycle, the adsorption process is a critical unit operation that has a significant impact on downstream processes and, ultimately, the quality of the final products. The development of a rapid method to determine the endpoints of adsorption processes in a large-scale manufacturing is of substantial importance for herbal medicine (HM) manufacturers. Methods: In this study, the adsorption of saponins on a macroporous resin column chromatograph, a critical unit operation in Panax notoginseng (Burkill) F.H.Chen injection manufacturing, was considered as an example. The evaluation results of in-line ultraviolet and visible spectra combined with various multivariate analysis methods, including the moving block standard deviation (MBSD), difference between the moving block average and the target spectrum (DMBA-TS), soft-independent modeling of class analogy (SIMCA), and partial least-squares discriminant analysis (PLS-DA), were compared. Results: MBSD was unsuitable for adsorption processes. The relative standard errors of prediction between the predicted and experimental endpoints were 13.2%, 4.67%, and 5.71% using DMBA-TS, SIMCA, and PLS-DA, respectively. Conclusions: Among the considered analysis methods, SIMCA and PLS-DA were more effective for endpoint determination. The results of this study provide a more comprehensive overview of the effectiveness of various multivariate analysis methods to facilitate the selection of the most suitable method. This study was also conducive to address the issues of the in-line detection of adsorption endpoints to guide practical HM manufacturing. Graphical abstract: http://links.lww.com/AHM/A23

Quantification of Salicylates and Flavonoids in Poplar Bark and Leaves Based on IR, NIR, and Raman Spectra.

Poplar bark and leaves can be an attractive source of salicylates and other biologically active compounds used in medicine. However, the biochemical variability of poplar material requires a standardization prior to processing. The official analytical protocols used in the pharmaceutical industry rely on the extraction of active compounds, which makes their determination long and costly. An analysis of plant materials in their native state can be performed using vibrational spectroscopy. This paper presents for the first time a comparison of diffuse reflectance in the near- and mid-infrared regions, attenuated total reflection, and Raman spectroscopy used for the simultaneous determination of salicylates and flavonoids in poplar bark and leaves. Based on 185 spectra of various poplar species and hybrid powdered samples, partial least squares regression models, characterized by the relative standard errors of prediction in the 4.5–9.9% range for both calibration and validation sets, were developed. These models allow for fast and precise quantification of the studied active compounds in poplar bark and leaves without any chemical sample treatment.

Multi critical quality attributes monitoring of Chinese oral liquid extraction process with a spectral sensor fusion strategy

The traditional Chinese medicine (TCM) extraction process is a complicated dynamic system with many variables and disturbance. Therefore, multi critical quality attributes (CQAs) monitoring is of great significance to understand the whole process. Spectroscopy is a powerful process analytical tool used for process understanding. However, single senor sometimes could not provide comprehensive information. Sensor fusion is a very practical method to overcome this deficiency. In this study, the extraction process of Xiao’er Xiaoji Zhike Oral Liquid (XXZOL) was carried out in pilot scale, where near infrared (NIR) spectroscopy and mid infrared (MIR) spectroscopy were collected to determine the concentrations of seven CQAs (synephrine, arecoline, chlorogenic acid, forsythoside A, naringin, hesperidin and neohesperidin) during extraction process. Based on fused data blocks, fusion partial least squares (PLS) models were established. Two fusion data blocks are obtained from the concatenation of original spectra (low-level data fusion) and the concatenation of characteristic variables based on band selection (mid-level data fusion) respectively. The results indicated that for all seven analytes, the mid-level data fusion models were superior to the single spectral models, with the prediction performance significantly improved. Specifically, the coefficients of determination (Rp2 and Rt2) of NIR, MIR and fusion quantitative models were all higher than 0.95. The relative standard errors of prediction (RSEP) values were all within 10%, except for models of neohesperidin, which were 10.76%, 12.39%, 12.05%, 10.03% for NIR, MIR, low-level and mid-level models respectively. These results demonstrate that it is feasible to monitor the extraction process of Xiao’er Xiaoji Zhike Oral Liquid more accurately and rapidly by fusing NIR and MIR spectroscopy, and the proposed approach also has vital and valuable reference value for the rapid monitoring of the mixed decoction process of other TCM.

Application of near infrared spectroscopy to predict contents of various lactones in chromatographic process of Ginkgo Folium

This study established a method for rapid quantification of terpene lactone, bilobalide, ginkgolide C, ginkgolide A and ginkgolide B in the chromatographic process of Ginkgo Folium based on near infrared spectroscopy(NIRS). The effects of competitive adaptive reweighting sampling(CARS), random frog(RF), and synergy interval partial least squares(siPLS) on the performance of partial least squares regression(PLSR) model were compared to the reference values measured by HPLC. Among them, the correlation coefficients of prediction(Rp) of validation sets of terpene lactone, bilobalide, and ginkgolide C were all higher than 0.98, and the relative standard errors of prediction(RSEPs) were 5.87%, 6.90% and 6.63%, respectively. Aiming at ginkgolide A and ginkgolide B with relatively low content, the genetic algorithm joint extreme learning machine(GA-ELM) was used to establish the optimized quantitative analysis model. Compared with CARS-PLSR model, the CARS-GA-ELM models of ginkgolide A and ginkgolide B exhibited a reduction in RSEP from 15.65% to 8.52% and from 21.28% to 10.84%, respectively, which met the needs of quantitative ana-lysis. It has been proved that NIRS can be used for the rapid detection of various lactone components in the chromatographic process of Ginkgo Folium.

Modeling of Antioxidant Activity, Polyphenols and Macronutrients Content of Bee Pollen Applying Solid-State 13C NMR Spectra.

An application of solid 13C nuclear magnetic resonance (NMR) spectroscopy for the determination of macronutrients, total polyphenols content, antioxidant activity, N C S elements, and pH in commercially available bee pollens is reported herein. Solid-state 13C NMR spectra were recorded for homogenized pollen granules without chemical treatment or dissolution of samples. By combining spectral data with the results of reference analyses, partial least squares models were constructed and validated separately for each of the studied parameters. To characterize and compare the models’ quality, the relative standard errors of prediction (RSEP) were calculated for calibration and validation sets. In the case of the analysis of protein, fat and reducing sugars, these errors were in the 1.8–2.5% range. Modeling the elemental composition of bee pollen on the basis of 13C NMR spectra resulted in RSEPcal/RSEPval values of 0.3/0.6% for the sum of NHCS elements, 0.3/0.4% for C, 1.8/1.9% for N, and 4.2/6.1% for S quantification. Analyses of total phenolics and ABTS antioxidant activity resulted in RSEP values in the 2.7–3.5% and 2.8–3.8% ranges, respectively, whereas they were 1.4–2.1% for pH. The obtained results demonstrate the usefulness of 13C solid-state NMR spectroscopy for direct determination of various important physiochemical parameters of bee pollen.

Near infrared spectroscopy determination of chemical and sensory properties in tomato

Fast and massive characterization of quality attributes in tomatoes is a necessary step toward its improvement; for sensory attributes this process is time-consuming and very expensive, which causes its absence in routine phenotpying. We aimed to assess the feasibility of near infrared (NIR) spectroscopy as a fast and economical tool to predict both the chemical and sensory properties of tomatoes. We built partial least squares models from spectra recorded from tomato puree and juice in 53 genetically diverse varieties grown in two environments. Samples were divided in calibration (210 samples for chemical traits, 45 samples for sensory traits) and validation sets (60 and 10, respectively) using the Kennard Stone algorithm. Models from puree spectra gave validation r2 values higher than 0.97 for fructose, glucose, soluble solids content, and dry matter (relative standard error of prediction, RSEP% ranged 3.5–5.8), while r2 values for sensory properties were lower (ranging 0.702–0.917 for taste-related traits (RSEP%: 9.1–20.0), and 0.009–0.849 for texture related traits (RSEP%: 3.6–72.1)). For sensory traits such as explosiveness, juiciness, sweetness, acidity, taste intensity, aroma intensity, and mealiness, NIR spectroscopy is potentially useful for scanning large collections of samples to identify likely candidates to select for tomato quality.

API Content and Blend Uniformity Using Quantum Cascade Laser Spectroscopy Coupled with Multivariate Analysis.

The process analytical technology (PAT) initiative proposed by the US Food and Drug Administration (FDA) suggests innovative methods to better understand pharmaceutical processes. The development of analytical methods that quantify active pharmaceutical ingredients (APIs) in powders and tablets is fundamental to monitoring and controlling a drug product’s quality. Analytical methods based on vibrational spectroscopy do not require sample preparation and can be implemented during in-line manufacturing to maintain quality at each stage of operations. In this study, a mid-infrared (MIR) quantum cascade laser (QCL) spectroscopy-based protocol was performed to quantify ibuprofen in formulations of powder blends and tablets. Fourteen blends were prepared with varying concentrations from 0.0% to 21.0% (w/w) API. MIR laser spectra were collected in the spectral range of 990 to 1600 cm−1. Partial least squares (PLS) models were developed to correlate the intensities of vibrational signals with API concentrations in powder blends and tablets. PLS models were evaluated based on the following figures of merit: correlation coefficient (R2), root mean square error of calibration, root mean square error of prediction, root mean square error of cross-validation, and relative standard error of prediction. QCL assisted by multivariate analysis was demonstrated to be accurate and robust for analysis of the content and blend uniformity of pharmaceutical compounds.

Nondestructive qualitative and quantitative analysis of Yaobitong capsule using near-infrared spectroscopy in tandem with chemometrics

The purpose of the study is to present a nondestructive qualitative and quantitative approach of hard-shell capsule using near-infrared (NIR) spectroscopy combined with chemometrics. The Yaobitong capsule (YBTC) was used for demonstration of the proposed approach and the NIR spectra were collected using a handheld fiber probe (FP) without the damage of capsule shell. By comparing the differences and similarities of the NIR spectra of capsule shells, contents and intact capsules, a preliminary conclusion can be drawn that the NIR spectra contained the information of the contents. Characteristic variables were selected by competitive adaptive weighted resampling (CARS) method, and least squares support vector machine (LSSVM) method based on particle swarm optimization (PSO) algorithm was applied to the construction of quantitative models. The relative standard error of prediction (RSEP) values of five saponins including notoginsenoside R1, ginsenoside Rg1, Re, Rb1, and Rd were 3.240%, 5.468%, 5.303%, 5.043%, and 3.745%, respectively. In addition, for qualitative model, three different types of adulterated capsules were designed. The model established by data driven version of soft independent modeling of class analogy (DD-SIMCA) demonstrated a satisfactory result that all adulterated capsules were identified accurately after an appropriate number of principal components (PCs) were chosen. The results indicated that although the NIR spectra collection was affected by capsule shell, sufficient content information can be obtained for quantitative and qualitative analysis after combining with chemometrics. It further proved that acquired NIR spectra do contain the effective component information of the capsule. This study provided a reference for the rapid nondestructive quality analysis of traditional Chinese medicine (TCM) capsule without damaging capsule shell.

Rapid determination of active components in Ginkgo biloba leaves by near infrared spectroscopy combined with genetic algorithm joint extreme learning machine

Near-infrared spectroscopy(NIRS) combined with band screening method and modeling algorithm can be used to achieve the rapid and non-destructive detection of the traditional Chinese medicine(TCM) production process. This paper focused on the ginkgo leaf macroporous resin purification process, which is the key technology of Yinshen Tongluo Capsules, in order to achieve the rapid determination of quercetin, kaempferol and isorhamnetin in effluent. The abnormal spectrum was eliminated by Mahalanobis distance algorithm, and the data set was divided by the sample set partitioning method based on joint X-Y distances(SPXY). The key information bands were selected by synergy interval partial least squares(siPLS); based on that, competitive adaptive reweighted sampling(CARS), successive projections algorithm(SPA) and Monte Carlo uninformative variable(MC-UVE) were used to select wavelengths to obtain less but more critical variable data. With selected key variables as input, the quantitative analysis model was established by genetic algorithm joint extreme learning machine(GA-ELM) algorithm. The performance of the model was compared with that of partial least squares regression(PLSR). The results showed that the combination with siPLS-CARS-GA-ELM could achieve the optimal model performance with the minimum number of variables. The calibration set correlation coefficient R_c and the validation set correlation coefficient R_p of quercetin, kaempferol and isorhamnetin were all above 0.98. The root mean square error of calibration(RMSEC), the root mean square error of prediction(RMSEP) and the relative standard errors of prediction(RSEP) were 0.030 0, 0.029 2 and 8.88%, 0.041 4, 0.034 8 and 8.46%, 0.029 3, 0.027 1 and 10.10%, respectively. Compared with the PLSR me-thod, the performance of the GA-ELM model was greatly improved, which proved that NIRS combined with GA-ELM method has a great potential for rapid determination of effective components of TCM.

Quantitative Determination of Vitamins A and E in Ointments Using Raman Spectroscopy

A quantitative analysis of vitamins A and E in commercial ointments containing 0.044% and 0.8% (w/w) of active pharmaceutical ingredients, respectively, was performed using partial least squares models based on FT Raman spectra. Separate calibration systems were prepared to determine the amount of vitamin A in a petrolatum base ointment and to quantify vitamins A and E in a eucerin base one. Compositions of the laboratory-prepared and commercial samples were controlled through a principal component analysis. Relative standard errors of prediction were calculated to compare the predictive ability of the obtained regression models. For vitamin A determination, these errors were found to be in the 3.8–5.0% and 5.7–5.9% ranges for the calibration and validation data sets, respectively. In the case of vitamin E modeling, these errors amounted to 3.7% and 4.4%. On the basis of elaborated models, vitamins A and E were successfully quantified in two commercial products with recoveries in the 99–104% range. The obtained data indicate that the Raman technique allows for accurate analysis of the composition of semisolid formulations in their native state, including low dose preparations.

Applications of Raman spectroscopy in art and archaeology

Applications of Raman spectroscopy in art and archaeology

De-risking excipient particle size distribution variability with automated robust mixing: Integrating quality by design and process analytical technology

BackgroundParticle size distribution (PSD) variability in excipients affects mixing. In response, manufacturers rely on raw material control and rigidly defined process parameters to achieve quality. However, this status quo is costly; and diverges from regulatory exceptions for process robustness. Although robustness improves cost and material usage efficiency, it remains under-adopted. MethodTo address this gap, a robust batch mixing operation that mitigated the impact of PSD variability was evaluated, with blends comprising chlorpheniramine, microcrystalline cellulose and lactose. PSD of lactose was varied to simulate commercially-relevant variability. Due to PSD-induced rheological variations, the blends had different optimal mixing speeds. For the automation study, near infrared (NIR) spectroscopy; process optimization and endpoint detection algorithms; and control hardware were integrated within a cluster of software environments. NIR spectroscopy was employed for in-line PSD characterization and blend monitoring, to modulate mixing speed and detect endpoint (feedforward and feedback control). ResultsNIR spectroscopy rapidly detected PSD variations by the 6th–9th rotations, to activate feedforward control, which mitigated the effect of PSD variability and reduced the mixing time by 13–34%. Endpoints were correctly detected. PSD variations and blend homogeneity were accurately predicted (relative standard error of prediction ≤ 2%). ConclusionThe automated robust mixing operation was successful. Pertinently, NIR spectrometer can be adopted for multimodal sensing. Its applicability for production-driven characterization of raw materials in batch and continuous pharmaceutical processing should be further explored. Lastly, this study laid the groundwork for end-to-end implementation of process analytical technology in robust batch processing.

Two Different Portables Visible-Near Infrared and Shortwave Infrared Region for On-Tree Measurement of Soluble Solid Content of Marian Plum Fruit

The goal of this study was to predict the soluble solid content (SSC) of on-tree Marian plum fruit using two different wavelength range and algorithm. One of these was the commercial dispersion NIR spectrometer (MicroNIR 1700), providing shortwave infrared (SWIR), while the other was a making diode array spectrometer giving visible-near infrared (Vis-NIR). To search optimal model, the analytical ability of the two wavelength ranges spectrometers coupled with two algorithms: i.e. partial least squares regression (PLSR) and support vector machine regression (SVR), were investigated. Different spectral pre-processing methods were tested. The model providing the lowest root mean square errors of prediction (RMSEP) was selected. Overall, the proposed outcome was that the performance of SWIR was more accurate than Vis-NIR spectrometer, and that both SWIR and Vis-NIR coupled with PLSR algorithm had a higher accuracy than SVR algorithm. The best model for on-tree evaluation SSC was the SWIR constructed using the PLSR algorithm with the spectral pre-processing of the 2nd derivative, providing a coefficient of determination of calibration set (R2) of 0.81, a coefficient of determination of validation set (r2) of 0.76, RMSEP of 0.69 °Brix, and a relative standard error of prediction (RSEP) of 4.43%. The outcome showed that a portable SWIR spectrometer developed with PLSR could be used for monitoring the SSC of individual Marian plum fruit on-tree for quality assurance.

A comparison between Box–Behnken design and artificial neural network: Modeling of removal of Phenol Red from water solutions by nanocobalt hydroxide

AbstractHere, we describe the successful removal of Phenol Red from aqueous solutions by nanocobalt hydroxide. Also two approaches, artificial neural network (ANN) and Box–Behnken design (BBD), are used to investigate predictive models for simulation and optimization of the dye removal process. The effect of process variables (such as pH, sorbent dosage, and Phenol Red concentration) on the removal efficiency are investigated through performing the BBD. A training set for ANN is obtained using the same design. Statistical values show ANN model is superior to BBD model. Based on the validation data set, ANN model has higher value of coefficient of determination (R2: 0.99 ANN > 0.84 BBD), lower values of root mean square error of prediction (RMSEP: 3.17 ANN < 3.99 BBD), mean square error (MSE: 10.08 ANN < 15.95 BBD), and relative standard error of prediction (REP: 3.89 ANN < 4.89 BBD). According to obtained results, ANN has better prediction performance in comparison with BBD. In addition, the maximum removal efficiency (%Rmax = 99.9) is found at the initial concentration of dye = 68.08 (mg/L), pH = 2.0, and sorbent mass = 9.57 g/L by performing the BBD.

Maintaining the predictive abilities of near-infrared spectroscopy models for the determination of multi-parameters in White Paeony Root

Near-infrared spectroscopy (NIRs) has been widely applied in the field of traditional Chinese medicine (TCM). However, the quality of TCM inevitably changes with time and origin, which will result in a decline in the prediction accuracy of constructed NIR models. In this study, models of White Paeony Root were maintained to ensure the accuracy of the predictive values of new samples. The applicability of the original models to the new samples were validated by principal component analysis and model evaluation indexes. Chemometric methods including spectral subtraction correction (SSC) and hierarchical cluster analysis-recalibration (HCA-RC) were introduced to maintain the constructed models. The results demonstrated that, according to the performances of the models, the model maintenance ability of HCA-RC was stronger than that of SSC. With the application of HCA-RC, relative standard error of prediction of moisture, albiflorin and paeoniflorin content were reduced from 5.650%, 29.83% and 39.89% to 2.350%, 14.23% and 14.57%, respectively. This result revealed that HCA-RC could better extract common features from historical and new batches of samples. In addition, the updated HCA-RC models can still be applied for the rapid detection of White Paeony Root. Model maintenance ameliorated the problems of the original models that occurred after a period of application. The updated models contained the characteristics of new batches of samples, which had the potential for long-term continuous application and improved detection efficiency.

Quantitative models for detecting the presence of lead in turmeric using Raman spectroscopy

The current study presents a novel methodology to quantify lead in Turmeric using Raman spectroscopy. In this study, Partial Least Squares Regression (PLSR) was used for the quantification of lead. For calibration purposes, different amounts of lead were added to Turmeric samples encompassing a concentration range between 4 and 25 ​μg ​g−1. Since lead does not show any Raman band, for the purposes of this study, a complex was formed, its solvent was evaporated and the complex solid samples were registered with a Raman instrument. Raman measurements were performed in two different modes, -diffuse reflectance and transmission-. The PLSR models developed from Raman spectra of two data acquisition modes were evaluated in order to determine the suitability of both acquisition modes for quantifying lead content. The results indicated that diffuse reflectance showed better performance in terms of accuracy and robustness with a bias of 0.55 ​μg ​g−1, a relative standard error of prediction (RSEP) of 8.5% and a correlation between the predicted and reference values (R2) of 0.967. Despite the low lead concentration in the samples, the proposed model allows the quantification of the lead content in a fast and simple way.

Quantification of Ash and Moisture in Wheat Flour by Raman Spectroscopy

Wheat flour is widely used on an industrial scale in baked goods, pasta, food concentrates, and confectionaries. Ash content and moisture can serve as important indicators of the wheat flour’s quality and use, but the routinely applied assessment methods are laborious. Partial least squares regression models, obtained using Raman spectra of flour samples and the results of reference gravimetric analysis, allow for fast and reliable determination of ash and moisture in wheat flour, with relative standard errors of prediction of the order of 2%. Analogous calibration models that enable quantification of carbon, oxygen, sulfur, and nitrogen, and hence protein, in the analyzed flours, with relative standard errors of prediction equal to 0.1, 0.3, 3.3, and 1.4%, respectively, were built combining the results of elemental analysis and Raman spectra.