Impact of sample heterogeneity on the evaluation of uncertainty from sampling and analytical steps in pharmaceutical analysis.

Measurement uncertainty is a critical factor in the reliability of pharmaceutical analyses, since it directly affects batch acceptance and regulatory compliance. While analytical uncertainty has been extensively studied, uncertainty arising from sampling remains less explored. This study aims to address this gap by evaluating the contributions of sampling and analytical uncertainties to the overall uncertainty for acetaminophen tablets and oral solution.

Measurement uncertainty for <711> Dissolution tests using Monte Carlo methods - Uncertainties arising from sampling and analytical steps.

Background: The dissolution test is a critical quality control method in the pharmaceutical industry, primarily used to assess drug bioavailability and ensure the consistency of manufactured batches. This test simulates the release of the active ingredient in the body and verifies compliance with specifications through multiple stages (e.g.

Contamination by microplastics and sorbed organic pollutants in the surface waters of the Tietê River, São Paulo-SP, Brazil.

Microplastics (MPs) are particles between 1 μm and 5 mm in size, originating mainly from poor solid waste and effluent management, that can reach water bodies from various sources. In freshwater environments, the occurrence, distribution, and characterization of this new class of pollutants are still little explored, especially in Brazil. The aim of this study was to assess the occurrence of MPs, as well as the presence and concentration of polychlorinated biphenyls (PCBs) sorbed to these particles in the surface waters of the Tietê River - SP.

Simplified and Detailed Evaluations of the Uncertainty of the Measurement of Microbiological Contamination of Pharmaceutical Products.

Background: The control of the microbial contamination of pharmaceutical products (PP) is crucial to ensure their safety and efficacy. The validity of the monitoring of such contamination depends on the uncertainty of this quantification. Highly uncertain quantifications due to the variability of determinations or the magnitude of systematic effects affecting microbial growth or other analytical operations make analysis unfit for the intended use.

Nonparametric estimation of measurement uncertainty arising from sampling.

Background: Increasingly, measurement uncertainty has been used by pure and applied analytical chemistry to ensure decision-making in commercial transactions and technical-scientific applications. Until recently, it was considered that measurement uncertainty boiled down to analytical uncertainty; however, over the last two decades, uncertainty arising from sampling has also been considered. However, the second version of the EURACHEM guide, published in 2019, assumes that the frequency distribution is approximately normal or can be normalized through logarithmic transformations, without treating data that deviate from the normality.

Fatty Acid Profile and and sp. Load of Wild-Caught Seaweed Fly (Haliday, 1838) (Diptera: Anthomyiidae).

World aquaculture is expected to continue to grow over the next few decades, which amplifies the need for a higher production of sustainable feed ingredients for aquatic animals. Insects are considered good candidates for aquafeed ingredients because of their ability to convert food waste into highly nutritional biomass. However, commercially available terrestrial insect species lack long-chain polyunsaturated fatty acids (LC-PUFAs), which are essential biomolecules for marine cultured species.

How do physicochemical properties contribute to inhibitory activity of promising peptides against Zika Virus NS3 protease?

Context And Results: Flavivirus diseases' cycles, especially Dengue and Yellow Fever, can be observed all over Brazilian territory, representing a great health concern. Additionally, there are no drugs available in therapy. In this scenario, in silico methodologies were applied to obtain physicochemical properties, as well as to better understand the ligand-biological target interaction mode of 20 previously reported NS2B/NS3 protease inhibitors of Dengue virus.

Enhancing analytical development in the pharmaceutical industry: A DoE-QSRR model for virtual Method Operable Design Region assessment.

Recently, the pharmaceutical industry has increasingly adopted the Analytical Quality by Design (AQbD) approach for analytical development. To facilitate AQbD approach implementation in the development of chromatographic methods for determining cephalosporin antibiotics, an in silico tool capable of performing virtual DoEs was developed enabling to obtain virtual operable regions of method. To this end, the drugs cephalexin, cefazolin, cefotaxime and ceftriaxone were analyzed using four experimental designs, deriving a DoE-QSRR model and employing Monte Carlo method.

Measurement uncertainty for < 905 > Uniformity of Dosage Units tests using Monte Carlo and bootstrapping methods - Uncertainties arising from sampling and analytical steps.

Uniformity of dosage unit (UDU) test is widely used to assess the quality, safety, and effectiveness of dosage forms in unit doses. An increased variability of the amount of drug (API - Active Pharmaceutical Ingredient) in each dose unit may lead to low quality, unsafety, and ineffective medicines. The aim of this work was to evaluate the measurement uncertainty associated with the acceptance value (AV) using the Monte Carlo and Bootstrapping methods, as well as to estimate the risk of false decisions regarding compliance/non-compliance due to uncertainty.

Bioaccumulation and Depletion of the Antibiotic Sulfadiazine C in Lambari ().

Antibiotics are present in the environment, primarily due to their release through wastewater treatment plants, agricultural practices, and improper disposal of unused medications. In the environment, these drugs can be bioaccumulated by organisms and transferred along the food chain. This is a problem when considering the consumption of fish meat.

Measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets.

Dissolution is used to determine the rate and extent of drug release from the dosage form into a dissolution medium, which allow to assess the batch-to-batch variability. Considering that the dissolution test is used to predict the vivo performance of the drug as well, it is important to guarantee the quality and reliability of dissolution test results. The aim of this work was to evaluate the measurement uncertainty arising from sampling and analytical steps of dissolution test of prednisone tablets.

Development and optimization of a LC-MS/MS compatible method for quantification of losartan, hydrochlorothiazide and their impurities using AQbD approach and measurement uncertainty evaluation.

The concept of Analytical Quality by Design (AQbD) comes as a more robust, economical, and scientifically based alternative for analytical development, to the detriment of OFAT (one factor at a time). This new understanding applicable to analytical development is recommended since regulatory flexibility can be achieved and ensure more reliable results throughout the life of the product. This new approach was applied to develop an analytical procedure indicative of stability for a pharmaceutical product of association of Losartan Potassium and Hydrochlorothiazide, considered a potential first line for the treatment of hypertension.

Development and optimization of stability-indicating method of ethinylestradiol, levonorgestrel, and their main impurities using quality by design approach.

The association of Ethinylestradiol 0.03 mg and Levonorgestrel 0.15 mg is a hormonal contraceptive that combines estrogen and progestogen.

Besifloxacin Nanocrystal: Towards an Innovative Ophthalmic Preparation.

Bacterial conjunctivitis significantly impacts public health, including more than one-third of eye diseases reported worldwide. It is an infection caused by various aerobic and anaerobic bacteria and is highly contagious. Therefore, it has a high incidence of bacterial resistance to the antibiotics commonly used for treatment.

Effect of Polydextrose on the Growth of as Well as Lactic Acid and Bacteriocin-like Inhibitory Substances (BLIS) Production.

was cultivated in MRS medium supplemented or not with polydextrose under different conditions in order to evaluate its effect on cell growth, lactic acid and bacteriocin-like inhibitory substance (BLIS) production. Independent variables were pH (4.0, 5.

Conformity assessment of medicines containing antibiotics - A multivariate assessment.

Pharmaceutical products must meet quality requirements to ensure the efficacy and safety of pharmacological treatment. Non-compliance of medicines can cause economic losses and compromise the patient's health. In this work, the risks of false compliance/non-compliance decisions for parenteral antibiotics (cephalothin, ciprofloxacin and metronidazole) were evaluated on the basis of analytical results, measurement uncertainties and specification limits.

Definition of multivariate acceptance limits (guard-bands) applied to pharmaceutical equivalence assessment.

The quality assessment of medicines involves multiple compliance parameters, such as identity, dosage, purity, potency, content uniformity, disintegration time, dissolution rate, among others. The measurement uncertainty associated with a measured value can affect the conformity assessment and, consequently, it impacts decision-making. Even if the particular risks are acceptable, the total risk may be significantly high.

Hot-melt extrudability of amorphous solid dispersions of flubendazole-copovidone: An exploratory study of the effect of drug loading and the balance of adjuvants on extrudability and dissolution.

The FDA-approved anthelmintic flubendazole has shown potential to be repositioned to treat cancer and dry macular degeneration; however, its poor water solubility limits its use. Amorphous solid dispersions may overcome this challenge, but the balance of excipients may impact the preparation method and drug release. The purpose of this study was to evaluate the influence of adjuvants and drug loading on the development of an amorphous solid dispersion of flubendazole-copovidone by hot-melt extrusion.

Measurement uncertainty evaluation and risk of false conformity assessment for microbial enumeration tests.

Microbial enumeration tests are widely used to assess the microbiological quality of non-sterile pharmaceutical products. Despite of all efforts to guarantee the reliability of microbial enumeration tests, there will always be an uncertainty associated with the measured values, which can lead to false conformity/non-conformity decisions. In this work, we evaluated the measurement uncertainty using a bottom-up approach and estimate the consumer's or producer's risk due to the measurement uncertainty.

Risk of false pharmaceutical equivalence (non-equivalence) decisions due to measurement uncertainty.

The pharmaceutical equivalence between test (generic or similar) and reference medicine is evaluated through in vitro quality tests involving multiple compliance parameters. Despite efforts to ensure the reliability of the analytical results obtained in the pharmaceutical equivalence studies, measurement uncertainties lead to a risk of false decisions. Thus, the aim of this work was to evaluate the measurement uncertainties associated with the analytical results obtained in the pharmaceutical equivalence studies of different pharmaceutical forms and to estimate the risks of false decisions in the evaluation of pharmaceutical equivalence.

Measurement Uncertainty and Conformity Assessment Applied to Drug and Medicine Analyses - A Review.

Analytical results are often used in scientific research, industrial and clinical applications to support decision making. Despite all efforts to ensure the reliability of analytical results (including method validation, internal quality control, use of certified reference materials, proficiency tests, and ISO 17025 accreditation), there will always be an uncertainty associated with the measured value. The measurement uncertainty expresses the quality of the analytical result and allows the comparability between analytical results or between the measured value and the specification limit(s).

Essential oil-based dispersive liquid-liquid microextraction for the determination of N,N-dimethyltryptamine and β-carbolines in human plasma: A novel solvent-free alternative.

The present study describes the development of a novel solvent-free vortex-assisted dispersive liquid-liquid microextraction alternative based on a natural essential oil as extracting solvent (VA-EO-DLLME) for the determination of N,N-dimethyltryptamine (DMT), harmine (HRM), harmaline (HRL) and tetrahydroarmine (THH) (compounds found in the ayahuasca tea, a psychedelic plant preparation) in human plasma. After optimization through full factorial and Box-Behnken experimental designs, this VA-EO-DLLME followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was completely validated and applied to authentic plasma specimens. Sample preparation consisted in the addition of 60 mg of NaCl, 100 μL of borate buffer and 100 μL of Eucalyptus globulus essential oil to a 200 μL aliquot of human plasma.

Analytical Quality by Design as an Important Tool to Determine the Best Analytical Conditions for Isoniazid and Its Respective Succinylated Prodrug.

Background: Tuberculosis is a worldwide health concern and isoniazid is the most used and considered one of the most effective drugs for its treatment. The "quality" concept must be incorporated into the final pharmaceutical product, according to the quality by design (QbD) definition. Therefore, the determination of analytical test conditions is extremely important and the design of experiments (DoE) becomes a very useful tool.

Risk of false conformity assessment applied to automotive fuel analysis: A multiparameter approach.

The low-quality of automotive fuels may lead to the generation of pollutants harmful to both environmental and human health. The quality evaluation of automotive fuels requires a multiparameter conformity assessment, which may lead to an increased total risk of false conformity decisions even if all parameters comply with the acceptance limits. Thus, the aim of this work was to propose the establishment of multivariate acceptance limits in order to ensure a reduced total risk of false conformity decisions applied to automotive fuels analysis.

Safety and Photoprotective Efficacy of a Sunscreen System Based on Grape Pomace ( L.) Phenolics from Winemaking.

In winemaking, a large amount of grape pomace is produced that is rich in polyphenolics and highly beneficial for human health, as phenols are useful for skin ultraviolet (UV) protection. In this investigation, we evaluated the safety and clinical efficacy of a sunscreen system containing a grape pomace extract from L. as a bioactive ingredient.