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1.
Environ Sci Technol ; 58(12): 5512-5523, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38478581

RESUMO

The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.


Assuntos
Monitoramento Ambiental , Ostreidae , Preparações Farmacêuticas , Poluentes Químicos da Água , Animais , Humanos , Bromofeniramina/análise , China , Clorfeniramina/análise , Antagonistas dos Receptores Histamínicos/análise , Oceanos e Mares , Ostreidae/química , Preparações Farmacêuticas/análise , Prometazina/análise , Poluentes Químicos da Água/análise
2.
Sci Total Environ ; 923: 171359, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38438025

RESUMO

This study presents the first set of data on the removal of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (HRAs) and their transformation products in two Romanian wastewater treatment plants (WWTPs), as well as the impact of these organic pollutants on freshwater receiving effluents. The research investigated eight target pharmaceuticals and three metabolites using a newly developed and validated Liquid Chromatography - Mass Spectrometry (LC-MS/MS) method. The combined determination had a range of quantification limits varying from 0.13 ng/L to 0.18 ng/L for surface water and from 0.28 ng/L to 0.43 ng/L for wastewater. All analytes except cimetidine and 5-hydroxy-omeprazole were identified in water samples. The study found similar overall removal efficiencies for both WWTPs (43.2 % for Galati and 51.7 % for Ramnicu-Valcea). The research also showed that ranitidine and omeprazole could pose a low to high ecological risk to aquatic organisms. The findings suggest that the treatment stages used in the two Romanian WWTPs are insufficient to remove the target analytes completely, leading to environmental risks associated with the occurrence of pharmaceutical compounds in effluents and freshwater.


Assuntos
Monitoramento Ambiental , Preparações Farmacêuticas , Rios , Poluentes Químicos da Água , Cromatografia Líquida , Omeprazol , Preparações Farmacêuticas/análise , Medição de Risco , Rios/química , Romênia , Espectrometria de Massas em Tandem , Eliminação de Resíduos Líquidos , Água , Poluentes Químicos da Água/análise
3.
Rapid Commun Mass Spectrom ; 38(7): e9712, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38351666

RESUMO

RATIONALE: Azelastine HCl is a second-generation H1 -receptor antagonist approved by the US Food and Drug Administration (US FDA) for treating seasonal allergic rhinitis and non-allergic vasomotor rhinitis. This study encompasses the validation of a liquid chromatography-ultra violet photo diode array (LC-UV/PDA) method for the drug and its extension to liquid chromatography/quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS) studies for identification and characterization of various stress degradation products of the drug. METHODS: Stress degradation of azelastine HCl was undertaken under the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) prescribed conditions of hydrolytic, photolytic, oxidative, and thermal stress. The degraded drug solutions were analyzed using Ultra Performance Liquid Chromatography (UPLC) employing a C18 (100 × 4.6 mm; 2.6 µ, Kinetex) column by isocratic elution. Detection wavelength was 241 nm. The degradation products were identified and characterized using UPLC-MS/TOF studies, and an attempt was made to isolate one of the degradation products by solvent extraction. RESULTS: The drug was found to significantly degrade under acidic/alkaline/neutral photolytic, oxidative, and alkaline hydrolytic conditions. Six degradation products (I-VI) were identified through LC-Q/TOF-MS studies that were adequately resolved from the drug with the developed UPLC method. All degradation products (I-VI) were ionized in the total ion chromatogram (TIC) in the LC-MS studies, and these were identified and characterized, and the degradation pathway of the drug was postulated. One of the oxidation products isolated from the degraded drug solution was characterized through differential scanning calorimetry, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance spectral data. CONCLUSIONS: Six degradation products generated from stress degradation studies on azelastine HCl were adequately resolved through LC-UV/PDA studies followed by method validation. These were successfully identified and characterized through LC-Q/TOF-MS studies, and the degradation pathways for the generation of these products from the drug have been postulated.


Assuntos
Ftalazinas , Espectrometria de Massas em Tandem , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , 60705 , Preparações Farmacêuticas/análise , Estabilidade de Medicamentos , Hidrólise , Oxirredução , Cromatografia Líquida de Alta Pressão/métodos , Fotólise
4.
Phytochem Anal ; 35(1): 87-92, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37581346

RESUMO

INTRODUCTION: Nanoparticles are used in various fields such as chemistry, pharmacy, biotechnology, and food science since they provide higher sensitivity than traditional optical detection methods. Recently, synthesis of nanomaterials using green chemistry has become popular. Many phytochemical components are used in the synthesis of nanoparticles, including vitamins, proteins, polysaccharides, glycosides, essential oils and phenolic compounds. OBJECTIVE: A novel green nanotechnology-based method using quince seed mucilage (QSM) was designed for the determination of ascorbic acid in pharmaceutical preparations. QSM, a natural polysaccharide, was used as a bioreducing and stabilizing reagent in the proposed silver nanoparticle (SNP)-based method. METHOD: In the first stage of the developed method, silver(I) is reduced to silver(0) via QSM and spherical, homogeneous SNPs were prepared (QSM-SNPs). In the second stage of the developed method, SNPs nuclei were enlarged with the addition of ascorbic acid. The developed method was validated by performance parameters (linearity, recovery, and precision). Ascorbic acid determination was performed by measuring increase in absorbance at 420 nm. RESULTS: The limit of detection and limit of quantification for ascorbic acid were, respectively, found to be at 0.27 and 0.90 µM. The QSM-SNP-based method was successfully applied to effervescent tablets containing ascorbic acid. The standards of the excipients frequently used in pharmaceutical preparations did not interfere with the developed method. CONCLUSION: The developed QSM-SNP-based method satisfies the requirements of green nanotechnology. The developed QSM-SNP-based method is simple, fast, eco-friendly and low-cost.


Assuntos
Nanopartículas Metálicas , Rosaceae , Ácido Ascórbico/análise , Prata/análise , Prata/química , Nanopartículas Metálicas/química , Rosaceae/química , Sementes/química , Polissacarídeos/análise , Preparações Farmacêuticas/análise
5.
Drug Test Anal ; 16(2): 162-167, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37290775

RESUMO

Pediatric poisoning represents a serious problem all around the world. Abuse or neglect of children by adults must be highlighted in children exposed to drugs to which they would not normally have access. Usually, segmental hair analysis would allow in these contexts to determine whether the exposure was unique or repetitive. Hair and nail samples from a 9-month-old girl were received in our laboratory for analysis, after the child was hospitalized due to severe dehydration caused by her mother's neglect. At the admission, flecainide, an antiarrhythmic never prescribed to the child, was identified in the daughter urine. Using an LC-MS/MS method, flecainide tested positive in the child's hair at the following concentrations: 66 pg/mg (root to 1 cm), 61 pg/mg (1-2 cm), and 125 pg/mg (2-3 cm). Traces below the limit of quantification (1 pg/mg) were also present in the nail clippings. These concentrations are much lower than those obtained in adults under daily treatment. Given the different pharmacokinetic and dynamic parameters in children, the different rate of hair growth, and the greater porosity of the hair, which makes it more prone to external contamination, the interpretation of hair findings in children remains very complicated. In this case, it can be assumed that the presence of the drug in the urine indicates systemic incorporation and that administration had occurred for some months (three positive segments). The interpretation of hair tests from young children needs a global review of all the findings, as a positive result cannot stand alone to claim repetitive exposures.


Assuntos
Flecainida , Queratinas , Humanos , Criança , Recém-Nascido , Adulto , Feminino , Pré-Escolar , Lactente , Cromatografia Líquida , Espectrometria de Massas em Tandem , Preparações Farmacêuticas/análise , Detecção do Abuso de Substâncias/métodos
6.
Phys Chem Chem Phys ; 25(39): 26613-26622, 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37755431

RESUMO

The proper detection of drug molecules is key for applications that have an impact in several fields, ranging from medical treatments to industrial applications. In case of illegal drugs, their correct and fast detection has important implications that affect different parts of society such as security or public health. Here we present a method based on nanoscale sensors made of carbon nanotubes modified with dopants that can detect three types of drug molecules: mephedrone, methamphetamine and heroin. We show that each molecule produces a distinctive feature in the density of states that can be used to detect it and distinguish it from other types of molecules. In particular, we show that for semiconducting nanotubes the inclusion of molecules reduces the gap around the Fermi energy and produces peaks in the density of states below the Fermi energy at positions that are different for each molecule. These results prove that it is possible to design nanoscale sensors based on carbon nanotubes tailored with dopants, in such a way that they might be able to discriminate between different types of compounds and, especially, drug molecules whose proper recognition has important consequences in different fields.


Assuntos
Nanotubos de Carbono , Preparações Farmacêuticas , Preparações Farmacêuticas/análise
7.
AAPS PharmSciTech ; 24(6): 166, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552397

RESUMO

Exosomes are biological nanovesicles that are intrinsically loaded with thousands of biomacromolecules and are principally responsible for cell-to-cell communication. Inspired by the natural payload, they have been extensively investigated as drug delivery vehicles; however, the drug distribution, whether into or onto exosomes, is still debatable. In the present work, we have tried to investigate it systemically by selecting 5-fluorouracil (5-FU) (hydrophilic) and paclitaxel (PAC) (hydrophobic), drugs with very different physicochemical characteristics, for the loading to the exosomes. Exosomes were obtained from bovine milk, and the drugs were loaded using three different methods: incubation, sonication, and triton x-100. The particle size was found to be approximately 100 nm in all the cases; however, the highest drug loading was found in the sonication method. Fluorescence spectrophotometer, EDX analysis, EDX mapping, XPS, and XRD analysis indicated the possible presence of more drugs over the surface in the case of the incubation method. Drugs loaded by the sonication method had more controlled release than simple incubation and triton x-100. The method of drug loading had an insignificant effect on the cytotoxicity while in line with our previous observation, the combination (PAC and 5-FU) exhibited synergism as evidenced by ROS assay, colony formation assay, and mitochondrial membrane potential assay.


Assuntos
Exossomos , Preparações Farmacêuticas/análise , Linhagem Celular Tumoral , Exossomos/química , Octoxinol , Sistemas de Liberação de Medicamentos , Paclitaxel/farmacologia , Fluoruracila
8.
Luminescence ; 38(9): 1632-1638, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37417422

RESUMO

Avapritinib (AVP) was the first precision drug to be approved by the US Food and Drug Administration (FDA) in 2020 for patients suffering from metastatic gastrointestinal stromal tumors (GISTs) and progressive systemic mastocytosis. The analysis of AVP in pharmaceutical tablets and human plasma was then carried out using a fast, efficient, sensitive, and simple fluorimetric method using a fluorescamine reagent. The procedure is based on the interaction between fluorescamine as a fluorogenic reagent and the primary aliphatic amine moiety in AVP using borate buffer solution at pH 8.8. The produced fluorescence was measured at 465 nm (Excitation at 395 nm). The calibration graph's linearity range was discovered to be 45.00-500.0 ng mL-1 . Utilizing the International Council for Harmonization (ICH) and US-FDA recommendations, the research technique was validated and bioanalytically validated. The proposed approach was effectively employed for determining the stated pharmaceuticals in plasma with a high percentage of recovery ranging from 96.87 to 98.09 and pharmaceutical formulations with a percentage of recovery equal to 102.11% ± 1.05%. In addition, the study was extended to a pharmacokinetic study of AVP with 20 human volunteers as a step for AVP management in therapeutic cancer centers.


Assuntos
Fluorescamina , Humanos , Indicadores e Reagentes , Preparações Farmacêuticas/análise , Espectrometria de Fluorescência/métodos
9.
Sanid. mil ; 79(2): 111-117, jun. 2023.
Artigo em Espanhol | IBECS | ID: ibc-230413

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en febrero, marzo y abril de 2023 considerados de mayor interés para los profesionales sanitarios. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency issued in February, March and April 2023, and considered of interest to healthcare professionals, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)


Assuntos
Avaliação de Medicamentos , Preparações Farmacêuticas/análise
10.
Sanid. mil ; 79(2): 111-117, jun. 2023.
Artigo em Espanhol | IBECS | ID: ibc-EMG-596

RESUMO

Se reseñan los medicamentos evaluados y con dictamen positivo por comisión de expertos de la Agencia Española de Medicamentos y Productos Sanitarios o de la Agencia Europea del Medicamento hechos públicos en febrero, marzo y abril de 2023 considerados de mayor interés para los profesionales sanitarios. Se trata de opiniones técnicas positivas que son previas a la autorización y puesta en el mercado del medicamento. (AU)


The drugs assessed by the Spanish Agency for Medicines and Health Products or European Medicines Agency issued in February, March and April 2023, and considered of interest to healthcare professionals, are reviewed. These are positive technical reports prior to the authorization and placing on the market of the product. (AU)


Assuntos
Avaliação de Medicamentos , Preparações Farmacêuticas/análise
11.
Forensic Sci Int ; 347: 111678, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37030199

RESUMO

The use of the drug scopolamine in drug-facilitated crimes is known. Nevertheless, given the high potency of the drug and its rapid metabolism, analysis in blood and urine may not be sufficient for drug detection in late crime declaration, especially following a single-dose administration in drug-facilitated sexual assault (DFSA) cases. Hair may constitute an essential supplemental matrix extending the drug detection window in such cases. This case report presents quantitative data on scopolamine findings in urine and hair in a DFSA case. A young female had consumed several alcoholic drinks at a party venue when her behaviour became noticeably peculiar. Later, she woke up next to an unknown man and had no recollection of the night's events. Blood and urine samples were collected 18 h after the incident. The initial toxicological target screening using UHPLC-TOF-MS detected scopolamine in the hydrolysed urine sample, and quantification yielded 41 µg/L scopolamine in urine, while blood was negative. Segmental hair analysis using multitarget UHPLC-MS/MS was performed on three washed 2-cm segments of hair collected five weeks after the incident, yielding 0.37 pg/mg scopolamine only in the relevant hair segment. This case report provides novel insight into the concentration in hair following a single exposure of scopolamine and the feasibility of detecting scopolamine in hair by comparison to published toxicological findings.


Assuntos
Delitos Sexuais , Espectrometria de Massas em Tandem , Humanos , Masculino , Feminino , Preparações Farmacêuticas/análise , Escopolamina , Detecção do Abuso de Substâncias , Cabelo/química
12.
Forensic Toxicol ; 41(2): 260-271, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37060498

RESUMO

PURPOSE: Micro-segmental analysis (MSA), which enables the measurement of detailed drug distributions in hair by segmenting a single hair strand at 0.4 mm intervals, is indispensable for estimating the day of drug ingestion. However, haircare with dryers and various products can influence drug concentrations in hair. Therefore, the applicability of MSA to hair that was treated with heat or various haircare products was evaluated. METHODS: Reference hair strands containing drugs consistently along the hair shafts were collected from patients who ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) daily for 4 months. The hair strands were divided into eight 4 mm regions from the proximal end, and each region was placed on an electric hot plate at 100-200 °C or soaked in haircare products, such as shampoo and bleaching agent. The hair regions were subjected to MSA. Moreover, after a patient was administered midazolam at a single dose and the hair was bleached, the day of midazolam administration was estimated using MSA. RESULTS: Repetitive heating for 1 min and daily haircare products, such as shampoo, hardly affected the drugs in hair, whereas bleaching products containing H2O2 decreased the amounts of hay-fever medicines in the hair up to 58%. However, the amount of midazolam did not decrease in bleached hair and the day of midazolam administration was successfully estimated. CONCLUSIONS: The analytes used in this study were minimally affected by ordinary haircare and could be detected even in bleached hair. Therefore, MSA can be applicable regardless of haircare history.


Assuntos
Temperatura Alta , Midazolam , Humanos , Peróxido de Hidrogênio , Preparações Farmacêuticas/análise , Cabelo/química
13.
Biol Trace Elem Res ; 201(12): 5848-5860, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36964813

RESUMO

The use of medicinal plants for self-medication of minor health conditions has become a widespread practice in contemporary society. Few consumes, however, question the contamination of these products with toxic factors resulting from the planet's increasingly polluted environment. This paper presents the levels of five toxic elements (As, Cr, Pb, Cd, and Hg) and nine organochlorine pesticides (hexachlorobenzene (HCB), lindane, heptachor, aldrin, dieldrin, endrin, p,p'DDE, p,p'DDD, and p,p'DDT) in 14 brands of regularly consumed medicinal products in Romania. The toxic elements content was determined using energy-dispersive X-ray fluorescence (EDXRF) technique, and organochlorine pesticide residues (OPCs) were quantified using gas-chromatographic method, equipped with electron capture detector (GC-ECD). The results show that in the case of Cr, Cd, and Hg, the concentrations exceeded the limit values established by World Health Organisation (WHO) for raw herbal material. The higher level of OPCs (such as p,p'DDD, p,p'DDT, aldrin, and dieldrin) was found in the samples of Hypericum perforatum-St. John's wort, Crataegus monogyna-hawthorn, and Epilobium parviflorum-hoary willowherb. The correlations between the content of toxic elements and pesticides were determined by statistical analysis. Hierarchical clustering technique was used to detect natural grouping between the toxic elements and pesticides. For herb samples, four clusters were identified, the strongest correlated cluster consisting of Pb, HCB, Cr, and Hg. A further analysis within this cluster suggested that Cr levels are statistically different from the rest of the elements.


Assuntos
Mercúrio , Resíduos de Praguicidas , Praguicidas , Plantas Medicinais , Resíduos de Praguicidas/análise , Dieldrin/análise , DDT/análise , Plantas Medicinais/química , Aldrina/análise , Hexaclorobenzeno/análise , Cádmio/análise , Chumbo/análise , Praguicidas/análise , Mercúrio/análise , Preparações Farmacêuticas/análise
14.
Proc Natl Acad Sci U S A ; 120(7): e2215308120, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36745793

RESUMO

Drug delivery systems (DDSs) that can overcome tumor heterogeneity and achieve deep tumor penetration are challenging to develop yet in high demand for cancer treatment. We report here a DDS based on self-assembling dendrimer nanomicelles for effective and deep tumor penetration via in situ tumor-secreted extracellular vesicles (EVs), an endogenous transport system that evolves with tumor microenvironment. Upon arrival at a tumor, these dendrimer nanomicelles had their payload repackaged by the cells into EVs, which were further transported and internalized by other cells for delivery "in relay." Using pancreatic and colorectal cancer-derived 2D, 3D, and xenograft models, we demonstrated that the in situ-generated EVs mediated intercellular delivery, propagating cargo from cell to cell and deep within the tumor. Our study provides a new perspective on exploiting the intrinsic features of tumors alongside dendrimer supramolecular chemistry to develop smart and effective DDSs to overcome tumor heterogeneity and their evolutive nature thereby improving cancer therapy.


Assuntos
Dendrímeros , Vesículas Extracelulares , Neoplasias , Humanos , Preparações Farmacêuticas/análise , Dendrímeros/química , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Microambiente Tumoral
15.
Bioanalysis ; 15(1): 5-16, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36762451

RESUMO

Analysis of "free" drug/target concentrations is important to set up appropriate pharmacokinetic-pharmacodynamic models, to evaluate active-drug exposure and target engagement. Such "free-analyte" determination could be done by direct bioanalysis using an appropriate "free-analyte" assay. Development of "free" assays is often considered challenging from a technological and regulatory perspective. The application of a "total-total" approach, where the "free-analyte" concentration is determined mathematically, is considered a more convenient option. In this perspective, we examine and discuss the challenges of this "total-total" approach, from the affinity data, the importance of applying an appropriate "total" assay, the impact of additional binding partners and the variability of the total drug/target assays and their impact on the quality and variability of the final "free-analyte" dataset.


Assuntos
Preparações Farmacêuticas , Farmacocinética , Preparações Farmacêuticas/análise
16.
Biotechnol Adv ; 63: 108103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36702197

RESUMO

Protein-based nanocarriers are versatile and biocompatible drug delivery systems. They are of particular interest in nanomedicine as they can recruit multiple functions in a single modular polypeptide. Many cell-targeting peptides or protein domains can promote cell uptake when included in these nanoparticles through receptor-mediated endocytosis. In that way, targeting drugs to specific cell receptors allows a selective intracellular delivery process, avoiding potential side effects of the payload. However, once internalized, the endo-lysosomal route taken by the engulfed material usually results in full degradation, preventing their adequate subcellular localization, bioavailability and subsequent therapeutic effect. Thus, entrapment into endo-lysosomes is a main bottleneck in the efficacy of protein-drug nanomedicines. Promoting endosomal escape and preventing lysosomal degradation would make this therapeutic approach clinically plausible. In this review, we discuss the mechanisms intended to evade lysosomal degradation of proteins, with the most relevant examples and associated strategies, and the methods available to measure that effect. In addition, based on the increasing catalogue of peptide domains tailored to face this challenge as components of protein nanocarriers, we emphasize how their particular mechanisms of action can potentially alter the functionality of accompanying protein materials, especially in terms of targeting and specificity in the delivery process.


Assuntos
Endossomos , Nanopartículas , Endossomos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Endocitose , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/metabolismo , Nanopartículas/química
17.
J Anal Toxicol ; 47(2): 182-190, 2023 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35957494

RESUMO

The present study reports a thorough research on the stability of drugs of abuse and pharmaceuticals over a time period of 12 months. Fixed-liver tissues and formalin solutions where the tissues were preserved were analyzed using an ultra high performance liquid chromatography--tandem mass spectrometry method that has been developed and validated for this purpose. The method monitors 84 drugs in a 13-minute run. The concentrations of the drugs found were compared with their concentrations determined in the fresh liver tissues in a previous study. In the study, 14 cases with forensic interest were included with the main objective of the analysis and the study of the stability and the distribution of drugs of abuse and pharmaceuticals in the human liver and the formalin solution during preservation. The results showed that the number of detected compounds in the first month was significantly lower than the compounds found in fresh tissues. The effect of formalin was catalytic, and few substances could be detected. Specifically, out of the 86 positive detections of the monitored substances in the fresh tissues (in which 25 different substances were found), only 32 (37%) remained detectable 3 months after, 20 (23%) 6 months after and 15 (17%) 12 months after.


Assuntos
Formaldeído , Fígado , Humanos , Formaldeído/química , Cromatografia Gasosa-Espectrometria de Massas , Fígado/química , Espectrometria de Massas em Tandem , Preparações Farmacêuticas/análise
18.
ACS Biomater Sci Eng ; 9(6): 2819-2837, 2023 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-34784462

RESUMO

The gastrointestinal mucus layer plays a significant role in maintaining gut homeostasis and health, offering protective capacities against the absorption of harmful pathogens as well as commensal gut bacteria and buffering stomach acid to protect the underlying epithelium. Despite this, the mucus barrier is often overlooked during preclinical pharmaceutical development and may pose a significant absorption barrier to high molecular weight or lipophilic drug species. The complex chemical and physical nature of the dynamic mucus layer has proven problematic to reliably replicate in a laboratory setting, leading to the development of multiple mucus models with varying complexity and predictive capacity. This, coupled with the wide range of analysis methods available, has led to a plethora of possible approaches to quantifying mucus permeation; however, the field remains significantly under-represented in biomedical research. For this reason, the development of a concise collation of the available approaches to mucus permeation is essential. In this review, we explore widely utilized mucus mimics ranging in complexity from simple mucin solutions to native mucus preparations for their predictive capacity in mucus permeation analysis. Furthermore, we highlight the diverse range of laboratory-based models available for the analysis of mucus interaction and permeability with a specific focus on in vitro, ex vivo, and in situ models. Finally, we highlight the predictive capacity of these models in correlation with in vivo pharmacokinetic data. This review provides a comprehensive and critical overview of the available technologies to analyze mucus permeation, facilitating the efficient selection of appropriate tools for further advancement in oral drug delivery.


Assuntos
Sistemas de Liberação de Medicamentos , Muco , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Permeabilidade , Muco/química , Muco/microbiologia , Bactérias
19.
J Chromatogr Sci ; 61(7): 678-687, 2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35870199

RESUMO

The present study aimed to develop a validated RP-HPLC method for the simultaneous determination of timolol maleate (TM), moxifloxacin hydrochloride (MOXI), diclofenac sodium (DS) and dexamethasone (DEXA) in human plasma, bovine aqueous humor and pharmaceutical preparations. The chromatographic separation was studied using the C18 column. The chromatographic conditions, such as composition, pH, the flow rate of mobile phase, the temperature of column, wavelength of absorption and injection volume of the sample, were studied. The method was validated to confirm specificity, linearity and accuracy in accordance with an International Conference on Harmonization guidelines. The optimum conditions for separation included mobile phase 0.05 M monobasic phosphate buffer: acetonitrile (65:35 v/v), pH of buffer adjusted to 6.2 and the flow rate of 1 mL/minute. The optimum temperature of the column was found to be 35°C, absorption wavelength 265 nm and injection volume 50 µL. The baseline separation of all four drugs with good sensitivity, resolution, and a less than 15 min run time was achieved. The retention time of TM, MOXI, DS and DEXA were 4.3,5.7,9.9 and 13.5 minutes respectively. The limit of detection (LOD) values were 6.2, 4.8, 0.8 and 1.2 ng/mL for TM, MOXI, DS and DEXA, respectively, whereas their respective limit of quantification (LOQ) values was: were 42.6, 26.8, 5.6 and 6.2 ng/mL. The coefficient of variation for intra-day and inter-day were in the range of 0.32-1.57 and 1.29-3.07%, respectively. The method was found to be sensitive, precise and accurate in human plasma and bovine aqueous humor and can be applied for the quantification of these compounds in plasma, aqueous humor and pharmaceuticals.


Assuntos
Humor Aquoso , Timolol , Animais , Bovinos , Humanos , Timolol/análise , Timolol/química , Moxifloxacina/análise , Humor Aquoso/química , Diclofenaco/análise , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Preparações Farmacêuticas/análise , Dexametasona/análise
20.
Food Chem ; 399: 133958, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36027812

RESUMO

The aim of study was to optimize an QuEChERS extraction procedure for simultaneous determination of organic pollutants in aquaculture products. The QuEChERS extracts were measured using LC-HRMS. The target contaminants include 32 pesticides and 20 pharmaceuticals which have not been regulated for the products in Korea. The method was validated according to CODEX guideline (CAC/GL 71-2009). LOD and LOQ for all analytes ranged from 0.1 to 2 µg/kg and from 0.5 to 5 µg/kg, respectively. Intra-day (n = 5) and inter-day (n = 9) accuracy and precision were evaluated with the guideline. The validated method was applied to aquaculture products (n = 303). As a result, 14 pesticides and 8 pharmaceuticals were quantified. Fluxapyroxad, a fungicide frequently detected in domestic surface waters, was found with relatively higher concentration in 17 out of 23 species. It proves that a hydrophobic inland contaminant can be accumulated in the aquaculture products.


Assuntos
Poluentes Ambientais , Resíduos de Praguicidas , Praguicidas , Aquicultura , Poluentes Ambientais/análise , Resíduos de Praguicidas/análise , Praguicidas/análise , Preparações Farmacêuticas/análise , Espectrometria de Massas em Tandem/métodos
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