The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these assays. Both qPCR and dPCR are extensively used to answer bioanalytical questions for novel modalities such as cell and gene therapies. Following cross-industry conversations on the lack of information and guidelines for these assays, an American Association of Pharmaceutical Scientists working group was formed to address these gaps by bringing together 37 industry experts from 24 organizations to discuss best practices to gain a better understanding in the industry and facilitate filings to health authorities. Herein, this team provides considerations on assay design, development, and validation testing for PCR assays that are used in cell and gene therapies including (1) biodistribution; (2) transgene expression; (3) viral shedding; (4) and persistence or cellular kinetics of cell therapies.
- Keywords
- AAV, RT-qPCR, biodistribution, cell therapy, cellular kinetics, dPCR, gene therapy, qPCR, shedding, transgene expression,
- MeSH
- Genetic Therapy * MeSH
- Polymerase Chain Reaction MeSH
- Tissue Distribution MeSH
- Drug Development * MeSH
- Publication type
- Journal Article MeSH
The global situation related to the COVID-19 pandemic has forced employers to find an adequate way to conduct training in order to ensure work safety. The underground mining industry is one of the industries which, due to its nature, was not able to switch to remote work. Conducting traditional training risked spreading the virus among workers. For this purpose, it was necessary to start a search for a form of training that would be safe and would not cause additional stress for employees. Research on the development of an active employee training method and testing of the method itself was conducted online. In order to develop a method of active training, one of the most important workstations was selected, which is the operation of the conveyor belt. The training method comprises four training modules. The modules cover questions related to the operation of the conveyor belt, emergencies, its assembly and disassembly, repair and maintenance. The developed issues also take into account questions concerning natural hazards and work safety. The entire training course lasts 10 days. Every day, an employee receives a set of eight questions sent to their email address, which they must answer before starting work. The article describes the methodology and implementation of the training.
- Keywords
- active training method, human factor, occupational stress, underground mining, work safety,
- MeSH
- COVID-19 * MeSH
- Humans MeSH
- Pandemics * MeSH
- SARS-CoV-2 MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- MeSH
- Cognition * MeSH
- Humans MeSH
- Conditioning, Operant * MeSH
- Child, Preschool MeSH
- Child Development * MeSH
- Check Tag
- Humans MeSH
- Child, Preschool MeSH
- Publication type
- Journal Article MeSH
- Keywords
- Food safety, Isomers, Liquid chromatography tandem mass spectrometry, Method development, Pyrrolizidine alkaloids,
- Publication type
- Journal Article MeSH
Cotton-titania nanocomposites with multifunctional properties were synthesized through ultrasonic acoustic method (UAM). Ultrasonic irradiations were used as a potential tool to develop cotton-titania (CT) nanocomposites at low temperature in the presence of titanium tetrachloride and isopropanol. The synthesized samples were characterized by XRD, SEM, EDX and ICP-OES methods. Functional properties i.e. Ultraviolet protection factor (UPF), self-cleaning, washing durability, antimicrobial and tensile strength of the CT nanocomposites were evaluated by different methods. Central composite design and response surface methodology were employed to evaluate the effects of selected variables on responses. The results confirm the simultaneous formation and incorporation of anatase TiO2 with average crystallite size of 4nm on cotton fabric with excellent photocatalytic properties. The sustained self-cleaning efficiency of CT nanocomposites even after 30 home launderings indicates their excellent washing durability. Significant effects were obtained during statistical analysis for selected variables on the formation and incorporation of TiO2 nanoparticles (NPs) on cotton and photocatalytic properties of the CT nanocomposites.
- Keywords
- Nanocomposites, Self-cleaning, TiO(2), UPF, Ultrasonic acoustic method (UAM),
- Publication type
- Journal Article MeSH
The aim of this study was to develop benzydamine hydrochloride-loaded orodispersible films using the modification of a solvent casting method. An innovative approach was developed when the drying process of a small-scale production was used based on a heated inert base for casting the film. During this process, two types of film-forming maltodextrins for rapid drug delivery were used. They were plasticized with two different polyols (xylitol and sorbitol). Superdisintegrant Kollidon® CL-F was tested as an excipient that can induce faster disintegration of the prepared films. The influence of the formulation parameters (dextrose equivalent of film-forming maltodextrins, a type of plasticizer, and the presence of superdisintegrant) on the disintegration time, mechanical properties, and moisture content of films was statistically evaluated using a multivariate data analysis. Orodispersible films containing maltodextrin with lower dextrose equivalent value showed better mechanical properties (tensile strength ranged from 886.6 ± 30.2 to 1484.2 ± 226.9 N cm-2), lower moisture content (0.5 ± 0.0 to 1.2 ± 0.2%), and shorter disintegration time (17.6 ± 2.9 to 27.8 ± 2.8 s). Films plasticized with xylitol showed shorter disintegration time (17.6 ± 2.9 to 29.2 ± 3.8 s) than films containing sorbitol (23.8 ± 2.9 to 31.7 ± 3.9 s). With the addition of superdisintegrant Kollidon® CL-F, a significant influence on disintegration time was not observed. The modified solvent casting method shows great promise in a small-scale laboratory production of orodispersible films, e.g., in a pharmacy lab.
- Keywords
- benzydamine hydrochloride, maltodextrins, multivariate data analysis, orodispersible films, solvent casting method,
- MeSH
- Benzydamine chemistry MeSH
- Drug Delivery Systems * MeSH
- Polysaccharides chemistry MeSH
- Povidone chemistry MeSH
- Solvents chemistry MeSH
- Plasticizers chemistry MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Benzydamine MeSH
- maltodextrin MeSH Browser
- Polysaccharides MeSH
- Povidone MeSH
- Solvents MeSH
- Plasticizers MeSH
A capillary electrophoresis method for the simultaneous determination of the enantiomeric purity and of impurities of the chiral calcimimetic drug cinacalcet hydrochloride has been developed following Quality by Design principles. The scouting phase was aimed to select the separation operative mode and to identify a suitable chiral selector. Among the tested cyclodextrins, (2-carboxyethyl)-β-cyclodextrin and (2-hydroxypropyl)-γ-cyclodextrin (HPγCyD) showed good chiral resolving capabilities. The selected separation system was solvent-modified capillary zone electrophoresis with the addition of HPγCyD and methanol. Voltage, buffer pH, methanol concentration and HPγCyD concentration were investigated as critical method parameters by a multivariate strategy. Critical method attributes were represented by enantioresolution and analysis time. A Box-Behnken Design allowed the contour plots to be drawn and quadratic and interaction effects to be highlighted. The Method Operable Design Region (MODR) was identified by applying Monte-Carlo simulations and corresponded to the multidimensional zone where both the critical method attributes fulfilled the requirements with a desired probability π≥90%. The working conditions, with the MODR limits, corresponded to the following: capillary length, 48.5cm; temperature, 18°C; voltage, 26kV (26-27kV); background electrolyte, 150mM phosphate buffer pH 2.70 (2.60-2.80), 3.1mM (3.0-3.5mM) HPγCyD; 2.00% (0.00-8.40%) v/v methanol. Robustness testing was carried out by a Plackett-Burman matrix and finally a method control strategy was defined. The complete separation of the analytes was obtained in about 10min. The method was validated following the International Council for Harmonisation guidelines and was applied for the analysis of a real sample of cinacalcet hydrochloride tablets.
- Keywords
- Capillary electrophoresis, Chiral separation, Cinacalcet, Impurities, Method operable design region, Quality by Design,
- MeSH
- beta-Cyclodextrins chemistry MeSH
- Cinacalcet chemistry isolation & purification MeSH
- Electrophoresis, Capillary methods MeSH
- gamma-Cyclodextrins chemistry MeSH
- Risk Assessment MeSH
- Hydrogen-Ion Concentration MeSH
- Drug Contamination MeSH
- Monte Carlo Method MeSH
- Probability MeSH
- Solvents MeSH
- Stereoisomerism MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- beta-Cyclodextrins MeSH
- betadex MeSH Browser
- Cinacalcet MeSH
- gamma-Cyclodextrins MeSH
- gamma-cyclodextrin MeSH Browser
- Solvents MeSH
The aim of this study was to develop a simple extraction procedure and a multiresidual liquid chromatography-tandem mass spectrometry method for determination of a wide range of pharmaceuticals from various soil types. An extraction procedure for 91 pharmaceuticals from 13 soil types, followed by liquid chromatography-tandem mass spectrometry analysis, was optimized. The extraction efficiencies of three solvent mixtures for ultrasonic extraction were evaluated for 91 pharmaceuticals. The best results were obtained using acetonitrile/water (1/1 v/v with 0.1 % formic acid) followed by acetonitrile/2-propanol/water (3/3/4 v/v/v with 0.1 % formic acid) for extracting 63 pharmaceuticals. The method was validated at three fortification levels (10, 100, and 1000 ng/g) in all types of representative soils; recovery of 44 pharmaceuticals ranged between 55 and 135 % across all tested soils. The method was applied to analyze actual environmental samples of sediments, soils, and sludge, and 24 pharmaceuticals were found above limit of quantification with concentrations ranging between 0.83 ng/g (fexofenadine) and 223 ng/g (citalopram).
- Keywords
- Extraction efficiency, Extraction method, Liquid chromatography-tandem mass spectrometry, Matrix effects, Sediments, Sludge, Validation,
- MeSH
- 2-Propanol MeSH
- Acetonitriles MeSH
- Chromatography, Liquid methods MeSH
- Soil Pollutants analysis MeSH
- Pharmaceutical Preparations analysis MeSH
- Environmental Monitoring methods MeSH
- Sewage chemistry MeSH
- Soil chemistry MeSH
- Tandem Mass Spectrometry methods MeSH
- Publication type
- Journal Article MeSH
- Validation Study MeSH
- Names of Substances
- 2-Propanol MeSH
- acetonitrile MeSH Browser
- Acetonitriles MeSH
- Soil Pollutants MeSH
- Pharmaceutical Preparations MeSH
- Sewage MeSH
- Soil MeSH
