Confocal Raman Spectroscopic Imaging for Evaluation of Distribution of Nano-Formulated Hydrophobic Active Cosmetic Ingredients in Hydrophilic Films

Film-forming systems are highly relevant to the topical administration of active ingredients (AI) to the body. Enhanced contact with the skin can increase the efficacy of delivery and penetration during prolonged exposure. However, after the evaporation of volatile solvents to form a thin film, the distribution of the ingredient should remain homogenous in order to ensure the effectiveness of the formula. This is especially critical for the use of hydrophobic molecules that have poor solubility in hydrophilic films. In order to address this concern, hydroxyphenethyl esters (PHE) of Punica granatum seed oil were prepared as a nanosuspension stabilised by poloxamers (NanoPHE). NanoPHE was then added to a formulation containing polyvinyl alcohol (PVA) as a film forming agent, Glycerol as a plasticiser and an antimicrobial agent, SepicideTM HB. Despite their reliability, reference methods such as high-performance liquid chromatography are increasingly challenged due to the need for consumables and solvents, which is contrary to current concerns about green industry in the cosmetics field. Moreover, such methods fail to provide spatially resolved chemical information. In order to investigate the distribution of ingredients in the dried film, Confocal Raman imaging (CRI) coupled to Non-negatively Constrained Least Squares (NCLS) analysis was used. The reconstructed heat maps from a range of films containing systematically varying PHE concentrations highlighted the changes in spectral contribution from each of the ingredients. First, using NCLS scores it was demonstrated that the distributions of PVA, Glycerol, SepicideTM HB and PHE were homogenous, with respective relative standard deviations (RSD) of 3.33%, 2.48%, 2.72% and 6.27%. Second, the respective relationships between ingredient concentrations in the films and their Raman responses, and the spectral abundance were established. Finally, a model for absolute quantification for PHE was be constructed using the percentage of spectral abundance. The prepared %w/w concentrations regressed against predicted %w/w concentrations, displaying high correlation (R2 = 0.995), while the Root Mean Squared Error (0.0869% w/w PHE) confirmed the precision of the analysis. The mean percent relative error of 3.75% indicates the accuracy to which the concentration in dried films could be determined, further supporting the suitability of CRI for analysis of composite solid film matrix. Ultimately, it was demonstrated that nanoformulation of hydrophobic PHE provides homogenous distribution in PVA based film-forming systems independent of the concentration of NanoPHE used in the formula.

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Validation of a Method for Quantification of Lutein in Spinach Using High-Performance Liquid Chromatography: Interlaboratory Study

Journal of AOAC International ◽

10.1093/jaoacint/qsaa014 ◽

2020 ◽

Vol 103 (4) ◽

pp. 1073-1080

Author(s):

Takefumi Sonoda ◽

*Yusuke Hiejima ◽

Tomohiro Koiwa ◽

Masahiro Asano ◽

Eiichi Kotake ◽

...

Keyword(s):

High Performance Liquid Chromatography ◽

Liquid Chromatography ◽

High Performance ◽

Spinacia Oleracea ◽

The Body ◽

Interlaboratory Study ◽

Spinacia Oleracea L ◽

Study Results ◽

Relative Standard

Abstract Background Lutein is gaining attention as a strong antioxidant contained in foods. It accumulates in the human blood and retina, and is considered to play an important role in the body, especially in the eyes. Objective A method to determine the lutein content of raw spinach (Spinacia oleracea L.) was developed with the aim of its enactment as a Japanese agricultural standard (JAS) measurement method for components beneficial to human health. Methods An interlaboratory study was conducted to evaluate an analytical method for the determination of lutein in spinach. The detection limit and quantification limit of lutein for this method were 0.2 and 0.7 mg/kg, respectively. Twelve participating laboratories independently analyzed test samples (five pairs of blind duplicates) using high-performance liquid chromatography (HPLC). Results After removal of a few outliers, the repeatability relative standard deviation (RSDr), reproducibility (RSDR), and predicted RSDR of the evaluated method were 3.4–7.5, 4.6–13, and 7.5–8.5%, respectively, in a concentration range from 64.9–150 mg/kg. Conclusions The HorRat values (RSDR/predicted RSDR) of the lutein concentration were calculated to be 0.61–1.6. Highlights The study results indicate the acceptable precision of this method.

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Macroprobe Mode for the Study of Segregation in Steels

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100134909 ◽

1990 ◽

Vol 48 (2) ◽

pp. 260-261

Author(s):

Auclair Gilles ◽

Benoit Danièle

Keyword(s):

Mechanical Properties ◽

Spatial Distribution ◽

High Performance ◽

Volume Fraction ◽

Sheet Steel ◽

Acquisition Time ◽

Chemical Information ◽

X Ray ◽

Accurate Quantitative Analysis ◽

Optical Micrographs

During these last 10 years, high performance correction procedures have been developed for classical EPMA, and it is nowadays possible to obtain accurate quantitative analysis even for soft X-ray radiations. It is also possible to perform EPMA by adapting this accurate quantitative procedures to unusual applications such as the measurement of the segregation on wide areas in as-cast and sheet steel products.The main objection for analysis of segregation in steel by means of a line-scan mode is that it requires a very heavy sampling plan to make sure that the most significant points are analyzed. Moreover only local chemical information is obtained whereas mechanical properties are also dependant on the volume fraction and the spatial distribution of highly segregated zones. For these reasons we have chosen to systematically acquire X-ray calibrated mappings which give pictures similar to optical micrographs. Although mapping requires lengthy acquisition time there is a corresponding increase in the information given by image anlysis.

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ICH/FDA Guidelines-Compliant Validated Stability-Indicating HPLC-UV Method for the Determination of Axitinib in Bulk and Dosage Forms

Current Analytical Chemistry ◽

10.2174/1573411016999200802024151 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1106-1112

Author(s):

Ibrahim A. Darwish ◽

Nasr Y. Khalil ◽

Mohammad AlZeer

Keyword(s):

High Performance ◽

Kinase Inhibitor ◽

Degradation Products ◽

Internal Standard ◽

Dosage Forms ◽

Uv Detector ◽

Stability Indicating ◽

Therapeutic Benefits ◽

Relative Standard

Background: Axitinib (AXT) is a member of the new generation of the kinase inhibitor indicated for the treatment of advanced renal cell carcinoma. Its therapeutic benefits depend on assuring the good-quality of its dosage forms in terms of content and stability of the pharmaceutically active ingredient. Objective: This study was devoted to the development of a simple, sensitive and accurate stabilityindicating high-performance liquid chromatographic method with ultraviolet detection (HPLC-UV) for the determination of AXT in its bulk and dosage forms. Methods: Waters HPLC system was used. The chromatographic separation of AXT, internal standard (olaparib), and degradation products were performed on the Nucleosil CN column (250 × 4.6 mm, 5 μm). The mobile phase consisted of water:acetonitrile:methanol (40:40:20, v/v/v) with a flow rate of 1 ml/min, and the UV detector was set at 225 nm. AXT was subjected to different accelerated stress conditions and the degradation products, when any, were completely resolved from the intact AXT. Results: The method was linear (r = 0.9998) in the concentration range of 5-50 μg/ml. The limits of detection and quantitation were 0.85 and 2.57 μg/ml, respectively. The accuracy of the method, measured as recovery, was in the range of 98.0-103.6% with relative standard deviations in the range of 0.06-3.43%. The results of stability testing revealed that AXT was mostly stable in neutral and oxidative conditions; however, it was unstable in alkaline and acidic conditions. The kinetics of degradation were studied, and the kinetic rate constants were determined. The proposed method was successfully applied for the determination of AXT in bulk drug and dosage forms. Conclusions: A stability-indicating HPLC-UV method was developed and validated for assessing AXT stability in its bulk and dosage forms. The method met the regulatory requirements of the International Conference on Harmonization (ICH) and the Food and Drug Administration (FDA). The results demonstrated that the method would have great value when applied in quality control and stability studies for AXT.

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Development of an HPLC-UV Method for Quantification of Stattic

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180523092957 ◽

2019 ◽

Vol 15 (6) ◽

pp. 568-573

Author(s):

Soheil Sedaghat ◽

Ommoleila Molavi ◽

Akram Faridi ◽

Ali Shayanfar ◽

Mohammad Reza Rashidi

Keyword(s):

High Performance ◽

Accurate Method ◽

Plasma Samples ◽

Promising Target ◽

Relative Standard ◽

Dimerization Inhibitor ◽

Oncogenic Protein ◽

First Time ◽

Transcription 3

Background: Signal transducer and activator of transcription 3 (STAT3), an oncogenic protein found constitutively active in many types of human malignancies, is considered to be a promising target for cancer therapy. Objective: In this study for the first time, a simple and accurate method has been developed for the determination of a STAT3 dimerization inhibitor called stattic in aqueous and plasma samples. Methods: A reverse-phase high-performance liquid chromatography (RP-HPLC) composed of C18 column as stationary phase, and the mixture of acetonitrile (60%) and water (40%) as mobile phase with a UV detection at 215 nm were applied for quantification of stattic. The developed method was validated by Food and Drug Administration (FDA) guideline. Results: The method provided a linear range between 1-40 and 2.5-40 µg mL-1 for aqueous and plasma samples, respectively, with a correlation coefficient of 0.999. The accuracy (as recovery) of the developed method was found to be between 95-105% for aqueous medium and 85-115% for plasma samples. The precision (as relative standard deviation) for aqueous and plasma samples was less than 6% and 15%, respectively. The sensitivity of the developed method based on FDA guideline was 1 µg mL-1 for aqueous and 2.5 µg mL-1 for plasma samples. Conclusion: These results show that the established method is a fast and accurate quantification for stattic in aqueous and plasma samples.

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Calcium/Copper alginate framework doped with CuO nano-particles as a novel adsorbent for micro-extraction of benzodiazepines from human serum

Current Pharmaceutical Analysis ◽

10.2174/1573412916666200210150914 ◽

2020 ◽

Vol 16 ◽

Author(s):

Nadereh Rahbar ◽

Fatemeh Ahmadi ◽

Zahra Ramezani ◽

Masoumeh Nourani

Keyword(s):

Human Serum ◽

High Performance ◽

Limit Of Detection ◽

Solid Phase ◽

Nano Particles ◽

Limit Of Quantification ◽

Analytical Methodology ◽

Fiber Fabrication ◽

Relative Standard ◽

Green Procedure

Background: Sample preparation is one of the most challenging phases in pharmaceutical analysis, especially in biological matrices, affecting the whole analytical methodology. Objective: In this study, a new Ca(II)/Cu(II)/alginate/CuO nanoparticles hydrogel fiber (CCACHF) was synthesized through a simple, green procedure and applied for fiber micro solid phase extraction (FMSPE) of diazepam (DIZ) and oxazepam (OXZ) as model drugs prior to high-performance liquid chromatography-UV detection (HPLC-UV). Methods: Composition and morphology of the prepared fiber were characterized and the effect of main parameters on the fiber fabrication and extraction efficiency have been studied and optimized. Results: In optimal conditions, calibration curves were linear ranging between 0.1–500 µg L−1 with regression coefficients of 0.9938 and 0.9968. Limit of detection (LOD) (S/N=3) and limit of quantification (LOQ) (S/N=10) of the technique for DIZ and OXZ were 0.03 to 0.1 µg L−1. Within-day and between-day relative standard deviations (RSDs) for DIZ and OXZ were 6.0–12.5% and 3.3–9.4%, respectively. Conclusion: The fabricated adsorbent has been substantially employed to extraction of selected benzo-diazepines (BZDs) from human serum real specimens and the obtained recoveries were also satisfactory (82.1-109.7%).

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Evaluation of New 99mTc(CO)3 + Radiolabeled Glycylglycine In Vivo

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520619666190404154723 ◽

2019 ◽

Vol 19 (11) ◽

pp. 1382-1387

Author(s):

Ahmet M. Şenışık ◽

Çiğdem İçhedef ◽

Ayfer Y. Kılçar ◽

Eser Uçar ◽

Kadir Arı ◽

...

Keyword(s):

High Performance ◽

The Body ◽

Biological Behavior ◽

In Vivo Evaluation ◽

Radiolabeled Peptides ◽

Tumor Bearing ◽

Biodistribution Data ◽

Good Accordance ◽

Rapid Clearance

Background: Peptide-based agents are used in molecular imaging due to their unique properties, such as rapid clearance from the circulation, high affinity and target selectivity. Many of the radiolabeled peptides have been clinically experienced with diagnostic accuracy. The aim of this study was to investigate in vivo biological behavior of [99mTc(CO)3(H2O)3]+ radiolabeled glycylglycine (GlyGly). Methods: Glycylglycine was radiolabeled with a high radiolabeling yield of 94.69±2%, and quality control of the radiolabeling process was performed by thin layer radiochromatography (TLRC) and High-Performance Liquid Radiochromatography (HPLRC). Lipophilicity study for radiolabeled complex (99mTc(CO)3-Gly-Gly) was carried out using solvent extraction. The in vivo evaluation was performed by both biodistribution and SPECT imaging. Results: The high radiolabelling yield of 99mTc(CO)3-GlyGly was obtained and verified by TLRC and HPLRC as well. According to the in vivo results, SPECT images and biodistribution data are in good accordance. The excretion route from the body was both hepatobiliary and renal. Conclusion: This study shows that 99mTc(CO)3-GlyGly has the potential to be used as a peptide-based imaging agent. Further studies, 99mTc(CO)3-GlyGly can be performed on tumor-bearing animals.

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Simple HPLC-PDA Analysis to Determine Illegal Synthetic Dyes in Herbal Medicines

Applied Sciences ◽

10.3390/app11146641 ◽

2021 ◽

Vol 11 (14) ◽

pp. 6641

Author(s):

Kyung-Yuk Ko ◽

Eun-Young Choi ◽

Se-Hee Jeong ◽

Sohwa Kim ◽

Choon-Kil Lee ◽

...

Keyword(s):

High Performance ◽

Hplc Analysis ◽

Ammonium Acetate ◽

Herbal Medicines ◽

Positive Sample ◽

Array Detector ◽

Synthetic Dyes ◽

Sunset Yellow ◽

Herbal Medication ◽

Relative Standard

Various synthetic dyes are artificially added to herbal medicines for the purpose of visual attraction. In order to monitor the illegal usage of synthetic dyes in herbal medication, a rapid and straightforward analysis method to determine synthetic dyes is required. The study aimed to develop and validate a high-performance liquid chromatography (HPLC) analysis to determine ten synthetic dyes in Hawthorn fruit, Cornus fruit, and Schisandra fruit. Ten synthetic dyes such as Tartrazine, Sunset yellow, Metanil yellow, Auramine O, Amaranth, Orange II, Acid red 73, Amaranth, New Coccine, Azorubine, and Erythrosine B, were extracted using 50 mM ammonium acetate in 70% MeOH; then separated by gradient elution with a mobile phase consisting of acetonitrile and 50 mM ammonium acetate in distilled water using a photodiode array detector (PDA) at 428 nm or 500 nm. In addition, this study established the LC-MS/MS method to confirm the existence of synthetic dyes in the positive sample solution. The HPLC analysis had good linearity (r2 > 0.999). The recoveries of this method ranged from 74.6~132.1%, and the relative standard deviation (RSD) values were less than 6.9%. Most of the samples fulfilled the acceptance criteria of the AOAC guideline. This study demonstrates that the HPLC analysis can be applied to determine ten synthetic dyes in herbal medication.

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Analytical quality by design methodology for botanical raw material analysis: a case study of flavonoids in Genkwa Flos

Scientific Reports ◽

10.1038/s41598-021-91341-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Min Kyoung Kim ◽

Sang Cheol Park ◽

Geonha Park ◽

Eunjung Choi ◽

Yura Ji ◽

...

Keyword(s):

High Performance ◽

Quality By Design ◽

Analytical Data ◽

Gradient Elution ◽

Raw Material ◽

Analytical Quality ◽

Factor Screening ◽

Column Temperature ◽

Relative Standard ◽

Critical Method

AbstractThe present study introduces a systematic approach using analytical quality by design (AQbD) methodology for the development of a qualified liquid chromatographic analytical method, which is a challenge in herbal medicinal products due to the intrinsic complex components of botanical sources. The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for 11 flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peaks’ resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). The established chromatographic condition is as follows: acetonitrile and 0.1% formic acid gradient elution (0–13 min, 10–45%; 13–13.5 min, 45–100%; 13.5–14 min, 100–10%; 14–15 min, 10% acetonitrile), column temperature 28℃, detection wavelength 335 nm, and flow rate 0.35 mL/min using C18 (50 × 2.1 mm, 1.7 μm) column. A validation study was also performed successfully for apigenin 7-O-glucuronide, apigenin, and genkwanin. A few important validation results were as follows: linearity over 0.999 coefficient of correlation, detection limit of 2.87–22.41, quantitation limit of 8.70–67.92, relative standard deviation of precision less than 0.22%, and accuracy between 100.13 and 102.49% for apigenin, genkwanin, and apigenin 7-O-glucuronide. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug.

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Calculating the optimal hematocrit under the constraint of constant cardiac power

Scientific Reports ◽

10.1038/s41598-021-83427-2 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Michal Sitina ◽

Heiko Stark ◽

Stefan Schuster

Keyword(s):

Blood Flow ◽

High Performance ◽

Animal Species ◽

Normal Values ◽

Mechanical Load ◽

The Body ◽

Trade Off ◽

Cardiac Power ◽

Optimal Value ◽

Good Agreement

AbstractIn humans and higher animals, a trade-off between sufficiently high erythrocyte concentrations to bind oxygen and sufficiently low blood viscosity to allow rapid blood flow has been achieved during evolution. Optimal hematocrit theory has been successful in predicting hematocrit (HCT) values of about 0.3–0.5, in very good agreement with the normal values observed for humans and many animal species. However, according to those calculations, the optimal value should be independent of the mechanical load of the body. This is in contradiction to the exertional increase in HCT observed in some animals called natural blood dopers and to the illegal practice of blood boosting in high-performance sports. Here, we present a novel calculation to predict the optimal HCT value under the constraint of constant cardiac power and compare it to the optimal value obtained for constant driving pressure. We show that the optimal HCT under constant power ranges from 0.5 to 0.7, in agreement with observed values in natural blood dopers at exertion. We use this result to explain the tendency to better exertional performance at an increased HCT.

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