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1.
Molecules ; 26(11)2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34072538

RESUMO

The purpose of this review is to present an overview of roadside drug testing, driving enforcement, and drunk/drug driving detection around the world. Drunk and drug driving is a severe problem, not only in the UAE, but also around the world. This has important implications for road safety as drunk or drug driving may increase the chances of a driver's involvement in a road crash when compared to a drug-free driver. Recently, due to increases in drug-impaired drivers' crash involvement, many mobile roadside drug testing devices have been introduced to the market. These devices use oral fluid, urine or blood matrices. These are on-the-spot tests, which are easy to use and are applied by law enforcement agencies and the public. Law enforcement agencies most commonly use oral fluid to detect the presence of illicit drugs in drivers. This review discusses all the available devices in the market used by the authorities. It also describes the type of drugs widely abused by drivers along with behavioral testing methods. The different types of matrices used for roadside drug testing are also evaluated. Sample collection, storage, and pre-treatment methods are discussed, followed by the confirmatory analysis of positive samples. This article will significantly help law enforcement agencies compare and evaluate all the reliable roadside testing devices and new emerging confirmatory devices available to them in the market. This will help them make an informed decision on which device to adapt to their individual needs.


Assuntos
Intoxicação Alcoólica/diagnóstico , Drogas Ilícitas/análise , Testes Imediatos , Saliva/metabolismo , Detecção do Abuso de Substâncias/instrumentação , Detecção do Abuso de Substâncias/métodos , Acidentes de Trânsito/prevenção & controle , Condução de Veículo/legislação & jurisprudência , Dirigir sob a Influência/legislação & jurisprudência , Humanos , Drogas Ilícitas/efeitos adversos , Aplicação da Lei , Preparações Farmacêuticas/análise
2.
J Chromatogr A ; 1651: 462316, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34139386

RESUMO

CelerisTM Arginine (ARG) is a mixed-mode stationary phase recently released on the market. To characterize its analytical behavior, the retention factors of a pool (n=100, of which 36 neutrals, 26 acids and 38 bases) of pharmaceutically relevant compounds have been measured on this phase over eight percentages (from 10 to 90% v/v) of acetonitrile (MeCN) as organic modifier. The ARG phase exhibited enhanced affinity for the molecules that are in their anionic form at the experimental pH, whilst basic compounds, albeit over a wide range of lipophilicity and pKa values, were on average poorly retained. To dissect the separation mechanism of the ARG phase, the overall analytical retention has been deconvoluted into the individual contributions of intermolecular forces by a QSPR/ Partial Least Square (PLS)/Block Relevance (BR) analysis tool recently developed by us. For the neutrals, the most relevant blocks were found to be Size, describing the interaction due to the dimension of the molecule, and O, representing the solute's hydrogen bond donor properties. The change in sign from positive to negative of the Size block, which occurs between 10% and 20% MeCN, allowed to visually appreciate the switch in the separation mode from reversed phase to normal phase. Some good statistic models for rationalizing the analytical behaviour of neutrals were developed from VS+ descriptors. However, their performance in modelling the analytical retention of acids was substandard, probably due to the intrinsic inefficacy of VS+ descriptors in handling electric charges. This instance was addressed by a complimentary MLR strategy, which led to successfully model the retention of acids on the ARG column and to shed light into their retention mechanism, which seemed to be substantially driven by electrostatics.


Assuntos
Arginina/química , Preparações Farmacêuticas/análise , Cromatografia/métodos , Ligação de Hidrogênio , Análise dos Mínimos Quadrados , Análise de Componente Principal
3.
J Chromatogr A ; 1647: 462165, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33945931

RESUMO

This study presents a novel mixed-mode weak cation-exchange (WCX) material. This material was prepared by means of the functionalization of a mesoporous divinylbenzene (DVB) resin with maleic acid (maleic acid-DVB), which yielded a high carboxylic moiety content resulting in WCX interactions as well as suitable specific surface area for reversed-phase interactions. After the optimization of the solid-phase extraction (SPE) protocol to enhance the selectivity of the sorbent, this material was evaluated as a novel WCX sorbent in the SPE of a group of drugs from environmental water samples. The method is based on SPE followed by liquid chromatography (LC) coupled to high resolution mass spectrometry (HRMS) with an Orbitrap analyzer, and was validated and applied for the determination of basic drugs in river, effluent and influent wastewater samples. Maleic acid-DVB sorbent yielded suitable recovery rates (57% to 89%) and an acceptable matrix effect (<32%) thanks to the effective washing step included when these environmental waters were loaded through the novel resin. The method was applied to different environmental water samples and some basic drugs were suitably quantified in these environmental samples.


Assuntos
Maleatos/química , Extração em Fase Sólida/métodos , Águas Residuárias/química , Poluentes Químicos da Água/isolamento & purificação , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/isolamento & purificação , Poluentes Químicos da Água/análise
4.
J Chromatogr A ; 1649: 462225, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34038785

RESUMO

This study focused on the Analytical Quality by Design (AQbD) optimization of the chromatographic separation and mass spectrometric detection of a wide group of structurally heterogeneous model pharmaceutical compounds (PhCs) and transformation products (TPs), chosen to cover the challenging issues of the co-presence of compounds characterized by (i) a wide range of physicochemical properties, (ii) the same mass transitions, and (iii) different ionisation modes. Italian consumption of PhCs were also considered as election criteria of target analytes. Octadecyl and pentafluorophenyl stationary phases, acetonitrile/methanol ratios and acidity of the eluents, column temperature, initial organic phase percentage, and elution gradient were investigated by AQbD, aiming at optimizing critical resolutions, sensitivities, and analysis time. Statistically significant models were obtained in most cases with fitting and cross-validation coefficients in the ranges of 0.681-0.998 and 0.514-0.967, respectively. After optimization, the analysis of target analytes was performed in a single chromatographic run, adopting a mixed acquisition mode based on scheduled acquisition windows comprising both single polarity and continuous polarity switching. For most investigated analytes the method provided detection limits in the sub-ng/L to low ng/L range, meeting for macrolides the sensitivity requested by the "Watch List" 2018/840/EU. The optimized method was applied to the direct injection analysis of PhCs and TPs in four wastewater treatment plant (WWTP) effluents and surface water (SW) samples collected in the receiving water bodies. Absolute values of matrix effect were found to be far higher than 20% for most target analytes in most samples. Seventeen PhCs and two TPs were quantified in at least one sample, at the wide concentration range of about 1-3200 ng/L. The most occurring PhCs in both WWTP effluents and SWs were levofloxacin (202-1239 and 100-830 ng/L), furosemide (865-3234 and 230-880 ng/L), ketoprofen (295-1104 and 270-490 ng/L), and ibuprofen (886-3232 and 690-1440 ng/L).


Assuntos
Cromatografia Líquida/métodos , Preparações Farmacêuticas/análise , Espectrometria de Massas em Tandem/métodos , Poluentes Químicos da Água/análise , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Águas Residuárias/química
5.
Artigo em Inglês | MEDLINE | ID: mdl-34052556

RESUMO

Pharmaceutical compounds ingested by humans are metabolized and excreted in urine and feces. These metabolites can be quantified in wastewater networks using wastewater-based epidemiology (WBE) methods. Standard WBE methods focus on samples collected at wastewater treatment plants (WWTPs). However, these methods do not capture more labile classes of metabolites such as glucuronide conjugates, products of the major phase II metabolic pathway for drug elimination. By shifting sample collection more upstream, these unambiguous markers of human exposure are captured before hydrolysis in the wastewater network. In this paper, we present an HPLC-MS/MS method that quantifies 8 glucuronide conjugates in addition to 31 parent and other metabolites of prescription and synthetic opioids, overdose treatment drugs, illicit drugs, and population markers. Calibration curves for all analytes are linear (r2 > 0.98), except THC (r2 = 0.97), and in the targeted range (0.1-1,000 ng mL-1) with lower limits of quantification (S/N = 9) ranging from 0.098 to 48.75 ng mL-1. This method is fast with an injection-to-injection time of 7.5 min. We demonstrate the application of the method to five wastewater samples collected from a manhole in a city in eastern Massachusetts. Collected wastewater samples were filtered and extracted via solid-phase extraction (SPE). The SPE cartridges are eluted and concentrated in the laboratory via nitrogen-drying. The method and case study presented here demonstrate the potential and application of expanding WBE to monitoring labile metabolites in upstream wastewater networks.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glucuronídeos/análise , Preparações Farmacêuticas/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
6.
J Chromatogr A ; 1647: 462147, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33957347

RESUMO

Drug-induced phospholipidosis (DIPLD) represents a big concern for both regulatory authorities and pharmaceutical companies in drug discovery. Many researches pointed out that the negatively charged intralysosomal lipids play an important role in the formation of DIPLD. To better mimic this negatively charged lipid surface, a novel immobilized artificial membrane (IAM) column was prepared via in situ copolymerization of 12-methacryloyl n-dodecylphosphocholine (MDPC) and 12-methacryloyl n-dodecylphosphoric acid (MDPA). By introducing MDPA, the surface of the resulting monolithic column can be maintained negatively charged over a broad pH range. Scanning electron microscopy, elemental analysis and nano-HPLC experiments were carried out to characterize the physicochemical properties and chromatographic performance of the obtained monolithic IAM column. The results of ζ-potential and retention mechanism studies indicate that both hydrophobic and electrostatic interactions contribute greatly to the retention of cation analytes owing to the existence of the negatively charged MDPA under acidic conditions. To better assess the DIPLD potency of drug, the molar ratio between MDPC and MDPA in the monolithic column was carefully optimized. The results show that the poly(MDPC70PA30-co-EDMA) column has the best predictability with only two false-positives (donepezil, flecainide) in qualitative analysis of 61 drugs.


Assuntos
Doenças por Armazenamento dos Lisossomos/induzido quimicamente , Membranas Artificiais , Preparações Farmacêuticas , Fosfolipídeos , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Interações Hidrofóbicas e Hidrofílicas , Microscopia Eletrônica de Varredura , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Preparações Farmacêuticas/metabolismo , Ácidos Fosfatídicos , Fosfolipídeos/química , Fosfolipídeos/metabolismo , Eletricidade Estática
7.
Int J Mol Sci ; 22(8)2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33917733

RESUMO

Pharmaceutical drug development relies heavily on the use of Reversed-Phase Liquid Chromatography methods. These methods are used to characterize active pharmaceutical ingredients and drug products by separating the main component from related substances such as process related impurities or main component degradation products. The results presented here indicate that retention models based on Quantitative Structure Retention Relationships can be used for de-risking methods used in pharmaceutical analysis and for the identification of optimal conditions for separation of known sample constituents from postulated/hypothetical components. The prediction of retention times for hypothetical components in established methods is highly valuable as these compounds are not usually readily available for analysis. Here we discuss the development and optimization of retention models, selection of the most relevant structural molecular descriptors, regression model building and validation. We also present a practical example applied to chromatographic method development and discuss the accuracy of these models on selection of optimal separation parameters.


Assuntos
Cromatografia , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Farmacocinética , Relação Quantitativa Estrutura-Atividade , Algoritmos , Cromatografia/métodos , Análise de Dados , Cinética , Modelos Teóricos , Estudos de Validação como Assunto
8.
AAPS PharmSciTech ; 22(3): 128, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33835304

RESUMO

The adoption of Quality by Design (QbD) and Analytical Method Lifecycle Management (AMLM) concepts to ensure the quality of pharmaceutical products has been applied and proposed over the last few years. These concepts are based on knowledge gained from the application of scientific and quality risk management approaches, throughout method lifecycle to assure continuous improvement and high reliability of analytical results. The overall AMLM starts with the definition of the method's intended use through the Analytical Target Profile definition, including three stages: (1) Method Design, taking advantage of the well-known concept of QbD; (2) Method Performance Qualification; (3) Continued Method Performance Verification. This is intended to holistically align method variability with product requirements, increasing confidence in the data generated, a regulatory requirement that the pharmaceutical industry must follow. This approach views all method-related activities, such as development, validation, transfer, and routine use as a continuum and interrelated process, where knowledge and risk management are the key enablers. An increase in method robustness, cost reduction, and decreased risk failures are some of the intrinsic benefits from this lifecycle management. This approach is clearly acknowledged both by regulators and industry. The roadmap of the regulatory and industry events that mark the evolution of these concepts helps to capture the current and future expectation of the pharmaceutical framework.


Assuntos
Indústria Farmacêutica/normas , Preparações Farmacêuticas/análise , Química Farmacêutica , Desenho de Fármacos , Indústria Farmacêutica/tendências , Humanos , Controle de Qualidade
9.
Molecules ; 26(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918766

RESUMO

The analysis of controlled drugs in forensic matrices, i.e., urine, blood, plasma, saliva, and hair, is one of the current hot topics in the clinical and toxicological context. The use of microextraction-based approaches has gained considerable notoriety, mainly due to the great simplicity, cost-benefit, and environmental sustainability. For this reason, the application of these innovative techniques has become more relevant than ever in programs for monitoring priority substances such as the main illicit drugs, e.g., opioids, stimulants, cannabinoids, hallucinogens, dissociative drugs, and related compounds. The present contribution aims to make a comprehensive review on the state-of-the art advantages and future trends on the application of microextraction-based techniques for screening-controlled drugs in the forensic context.


Assuntos
Medicina Legal , Microextração em Fase Líquida/métodos , Preparações Farmacêuticas/análise , Microextração em Fase Sólida/métodos , Humanos , Drogas Ilícitas/análise
10.
J Chromatogr A ; 1645: 462085, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-33848654

RESUMO

Chirality control plays a critical role in developing stereoisomeric drugs. Due to the complexity and lack of predictability in chiral separations, column screening remains the gold standard to initiate chiral method development for active pharmaceutical ingredients (APIs) and synthetic intermediates. Chiral reversed-phase (RP) liquid chromatography (LC) has gained favor over other modes due to its versatility and compatibility in analyzing a wide range of chiral compounds in various matrices. Herein, we established a tier-based chiral RPLC screen strategy by constructing and analyzing a database of 101 chiral screens with a total of 3,401 entries (unique LC runs) for proprietary APIs or intermediates at Bristol Myers Squibb. Up to 17 polysaccharide-based chiral stationary phases (CSPs) and four mobile phases (MPs) have been screened with gradient elution. A selection of ten CSPs with two MPs was found sufficient to achieve successful separation for 82% of the total screens. Two RPLC screen tiers (Tier 1: AZ, OD, ID, and IG) and (Tier 2: AY, OJ, OZ, IA, IC, and IH) were proposed along with two MPs (acidic and neutral) to target ~70% hit rate for Tier 1, and ~80% for the combined set. We also implemented a user-friendly workflow to enable walk-up chiral RPLC screening with automated reports and system suitability tests.


Assuntos
Cromatografia de Fase Reversa/métodos , Preparações Farmacêuticas/análise , Polissacarídeos/química , Preparações Farmacêuticas/química , Preparações Farmacêuticas/isolamento & purificação , Estereoisomerismo
11.
Molecules ; 26(5)2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33668999

RESUMO

The present study aimed to assess the levels of 98 multi-class pharmaceuticals including cardiovascular drugs, antidepressants, hypnotics, antibiotics, and sulfonamides occurring in the muscle tissue of fish caught in the Baltic Sea. The following fish species were collected: perch (Perca fluviatilis); flounder (Platichthys flesus); turbot (Scophthalmus maximus); plaice (Pleuronectes platessa); cod (Gadus morhua callarias); bream (Abramis brama); crucian (Carassius carassius). Additionally, in the examined fish muscle the levels of heavy metals and trace elements were determined (As; Ag; Au; Ba; Cd; Co; Cr; Cu; Hg; Li; Mo; Ni; Pb; Sb; Se; Sn; Tl; V) as well as the levels of cholesterol and its 5 derivatives (7-ketocholesterol; 7α-hydroxycholesterol; 7ß-hydroxycholesterol; 5ß,6ß-epoxy-cholesterol; 5α,6α-epoxycholesterol). In the performed studies 11 out of 98 examined pharmaceuticals were detected in fish muscle. The levels of pharmaceuticals in fish muscle varied depending on the species. In the tissues of bream and crucian, no pharmaceuticals were found. Mercury, lead and arsenic were detected in the muscles of all examined fish. Based on the hazard factor for Hg, Pb, Cd, Ni (target hazard quotient, THQ < 1), it was found that the consumption of the studied fish does not constitute a health risk. However, the THQ for As remained >1 indicated possible risk from those metals. In the examined fish muscle the total cholesterol oxidation products (COPs) level of oxysterols were, respectively: 6.90 (cod) µg/g-4.18 µg/g (perch), which corresponded to 0.7-1.5% of cholesterol. The main COPs evaluated were 7-ketocholesterol (0.78 ± 0.14-1.79 ± 0.06 µg/g), 7ß-hydroxycholesterol (0.50 ± 0.04-3.20 ± 2.95 µg/g) and 5ß,6ß-epoxycholesterol (0.66 ± 0.03-1.53 ± 0.66 µg/g). The assessment of health hazards due to contaminations is necessary, which may help to introduce national legislation and global standards aimed at reducing or even eliminating the exposure to contaminants.


Assuntos
Metais Pesados/análise , Oxisteróis/análise , Preparações Farmacêuticas/análise , Animais , Peixes , Músculos/química , Preparações Farmacêuticas/metabolismo
12.
J Chromatogr A ; 1643: 462043, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33780879

RESUMO

An imaged capillary isoelectric focusing (icIEF) - UV fluorescence imaging detection method is described for the direct charge heterogeneity characterization of recombinant human erythropoietin (rhEPO) drug products (DPs). rhEPO is one of the most important protein therapeutics for biopharmaceutical industry worldwide. As a heavily glycosylated protein therapeutic, its charge heterogeneity must be carefully monitored in each step of manufacturing and storage. Current charge characterization methods suffer from challenges to characterize rhEPO DPs, due to low sensitivity of the method and potential for interference from the DP's formulation. The method described herein leverages the separation power of imaged cIEF separation combined with the increased sensitivity afforded by UV fluorescence imaging detection and requires no pre-treatment of the DP sample prior to analysis. The method was evaluated initially using a simulated DP, and subsequently a mini method validation was performed using a commercial rhEPO DP sample according to the guideline set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The limit of quantitation (LOQ) of the method is validated to be 20.3 IU/mL (or 0.10 µg/mL), which is approximately 100 times more sensitive than CZE - UV absorption detection method. To demonstrate the applicability of the method for use, 8 different commercial rhEPO DPs with concentrations ranging from 2000 IU/mL - 10,000 IU/mL were successfully evaluated. This method allows for sensitive, rapid analysis of low concentration rhEPO drug products without sample pre-treatment to provide critical charge heterogeneity information.


Assuntos
Eletroforese Capilar/métodos , Eritropoetina/análise , Focalização Isoelétrica/métodos , Preparações Farmacêuticas/análise , Raios Ultravioleta , Fluorescência , Humanos , Ligação Proteica , Proteínas Recombinantes/análise , Reprodutibilidade dos Testes
13.
Biomed Chromatogr ; 35(7): e5123, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33783841

RESUMO

Delivery of already existing and new drugs under development to the brain necessitates passage across the blood-brain barrier (BBB) with its tight intercellular junctions, molecular components and transporter systems. Consequently, it is critical to identify the extent of brain permeation and the partitioning across the BBB. The interpretation of brain-to-blood ratios is considered to be a significant and fundamental approach for estimating drug penetration through BBB, the brain-targeting ability and central nervous system (CNS) pharmacokinetics. Among the different bioanalytical techniques, liquid chromatography with various detectors has been widely used for determination of these ratios. This review defines the different approaches for sample preparation, extraction techniques and liquid chromatography procedures concerned with the determination of drugs in blood and brain tissues and the assessment of brain-to-blood levels. These approaches are expanded to cover the analysis of several drug classes such as CNS-acting drugs, chemotherapeutics, antidiabetics, herbal medicinal products, radiopharmaceuticals, antibiotics and antivirals. Accordingly, stability in biological matrices and matrix effects are investigated. The different administration/formulation effects and the possible deviations in these ratios are also disscussed.


Assuntos
Métodos Analíticos de Preparação de Amostras , Barreira Hematoencefálica , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/fisiologia , Encéfalo/metabolismo , Química Encefálica , Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/metabolismo , Farmacocinética , Manejo de Espécimes , Espectrofotometria Ultravioleta
14.
Anal Bioanal Chem ; 413(10): 2779-2791, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33770207

RESUMO

Mass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 µg/g tissue, R2 0.97 and 0.98 linearity, relative standard deviation QC <13.6%, and 97-112% accuracy. Other MS modes resulted in LOD 6.7-569.4 and 2.6-119.1 µg/g tissue, R2 0.86-0.98 and 0.86-0.98 linearity, relative standard deviation QC < 19.4 and < 37.5%, and 70-356% and 64-398% accuracy for drug candidates A and B, respectively. In addition, we propose an optimized 3D printed mimetic tissue model to increase the overall analytical throughput of our approach for large animal studies. The MRM imaging platform was applied as proof-of-principle for quantitative detection of drug candidates A and B in four dog livers and compared to LC-MS. The Q-MSI concentrations differed <3.5 times with the concentrations observed by LC-MS. Our presented MRM-based Q-MSI approach provides a more selective and high-throughput analytical platform due to MRM specificity combined with an optimized 3D printed mimetic tissue model.


Assuntos
Fígado/química , Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Animais , Cães , Limite de Detecção , Fígado/metabolismo , Espectrometria de Massas/instrumentação , Preparações Farmacêuticas/metabolismo
15.
J Chromatogr A ; 1639: 461919, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33535114

RESUMO

The first CE methodology enabling the enantiomeric separation of panthenol was developed in this work. Electrokinetic chromatography with cyclodextrins (CD-EKC) was the CE mode employed for this purpose. The effect of different experimental variables such as the nature and concentration of the cyclodextrin, the temperature and the separation voltage was investigated. The best enantiomeric separation was obtained with 25 mM (2-carboxyethyl)-ß-CD (CE-ß-CD) in 100 mM borate buffer (pH 9.0), with a separation voltage of 30 kV and a temperature of 30 °C. Under these conditions, an enantiomeric resolution of 2.0 in an analysis time of 4.2 min was obtained, being the biologically active enantiomer d-panthenol (dexpanthenol) the second-migrating enantiomer. The analytical characteristics of the method were evaluated in terms of precision, accuracy, selectivity, linearity, LOD, and LOQ, showing a good performance for the quantitation of dexpanthenol in cosmetic and pharmaceutical formulations. The enantiomeric impurity (L-panthenol) could be detected at a 0.1% level with respect to the majority enantiomer, allowing to accomplish the requirements of the ICH guidelines. The method was also successfully applied to study the stability of panthenol under abiotic and biotic conditions and its toxicity on non-target organisms (the aquatic plant Spirodela polyrhiza).


Assuntos
Eletroforese Capilar/métodos , Ácido Pantotênico/análogos & derivados , Testes de Toxicidade , Araceae/efeitos dos fármacos , Cromatografia , Cosméticos/análise , Ciclodextrinas/química , Limite de Detecção , Ácido Pantotênico/química , Ácido Pantotênico/isolamento & purificação , Ácido Pantotênico/toxicidade , Preparações Farmacêuticas/análise , Estereoisomerismo
16.
Mar Drugs ; 19(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530360

RESUMO

Biotechnology is an essential tool for the sustainable exploitation of marine resources, although the full development of their potential is complicated by a series of cognitive and technological limitations. Thanks to an innovative systematic approach that combines the meta-analysis of 620 articles produced worldwide with 29 high TRL (Technology Readiness Level) European funded projects, the study provides an assessment of the growth prospects of blue biotechnologies, with a focus on pharmaceutical and food applications, and the most promising technologies to overcome the main challenges in the commercialization of marine products. The results show a positive development trend, with publications more than doubled from 2010 (36) to 2019 (70). Biochemical and molecular characterization, with 150 studies, is the most widely used technology. However, the emerging technologies in basic research are omics technologies, pharmacological analysis and bioinformatics, which have doubled the number of publications in the last five years. On the other hand, technologies for optimizing the conditions of cultivation, harvesting and extraction are central to most business models with immediate commercial exploitation (65% of high-TRL selected projects), especially in food and nutraceutical applications. This research offers a starting point for future research to overcome all those obstacles that restrict the marketing of products derived from organisms.


Assuntos
Biotecnologia/métodos , Indústria Farmacêutica/métodos , Tecnologia de Alimentos/métodos , Biologia Marinha/métodos , Marketing/métodos , Animais , Biotecnologia/tendências , Biologia Computacional/métodos , Biologia Computacional/tendências , Indústria Farmacêutica/tendências , Tecnologia de Alimentos/tendências , Humanos , Biologia Marinha/tendências , Marketing/tendências , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-33477099

RESUMO

High quality chromatographic separation underpins robustness in LC-MS, frequently the analytical method of choice for pharmaceutical drug discovery work. The potential improvements in chromatographic selectivity afforded by serial column coupling (SCC), provide a useful means to enhance the resolution of complex samples. In this work, we present a revised high-throughput form of SCC, in which just two individual mixed phase columns were coupled together and combined with a gradient-optimised, retention-directed ultra-high pressure method to achieve rapid separations, with no further method optimisation necessary. The overall performance was evaluated from an open access DMPK analytical working environment perspective; where in anticipation of bioanalytical or metabolite identification chromatography challenges, or with the knowledge that stronger resolution was required for in-vitro sample analysis, the methodology could be immediately implemented by the analyst. Retention-directed selection of a shallow SCC gradient method was successful in separating peaks throughout the chromatographic window, resulting in a runtime still congruent to high-throughput analyses (3.5 min). In-vitro assay sample interferences were resolved 44-72% of the time, and the overall resolving power for isomeric separations significantly improved against single column comparisons (1.7-fold mean RS improvement). Over a sustained period of time in our laboratory, SCC methods have been used for metabolite identification and bioanalytical samples, where both convenience and effectiveness in solving analytical challenges has been consistently demonstrated. Examples that highlight SCC chromatography, and a guided discussion of the main high-throughput considerations, are included. The technique offers wide applicability, and we would recommend it as a toolbox consideration to the laboratory analyst.


Assuntos
Cromatografia Líquida/métodos , Preparações Farmacêuticas/análise , Preparações Farmacêuticas/química , Espectrometria de Massas em Tandem/métodos , Ensaios de Triagem em Larga Escala , Isomerismo
19.
Analyst ; 146(2): 365-381, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33231578

RESUMO

Porphyrins and phthalocyanines are promising π-conjugated compounds with fantastic photochemical and electrochemical properties which are present in nature in more systems than we are generally aware. The electrochemical properties of these large aromatic molecules are also unique, endowing them with the ability to catalyze a wide range of redox reactions. The macrocycle core of these molecules is extremely favorable for the complexation of several metal ions, resulting in molecules with tunable properties. Porphyrins and phthalocyanines are able to form highly organized films, with high conductivity and great robustness and their use was explored to build a great number of electrochemical and photoelectrochemical sensors for many varied applications, one among them being drug analysis. This review will focus on the potential of the electrodes modified with attractive porphyrins and phthalocyanines for this application. The papers published in the last 3 years were closely evaluated.


Assuntos
Eletroquímica/métodos , Indóis/química , Compostos Macrocíclicos/química , Preparações Farmacêuticas/análise , Porfirinas/química
20.
J Forensic Sci ; 66(2): 677-686, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33227173

RESUMO

In forensic contexts of advanced decomposition, when conventional matrices are no longer available for toxicological analyses, finding alternative matrices is necessary. The skeleton, which is fundamental for anthropologists and geneticists, could be useful also for toxicological purposes. The present study aims to examine what kind of information toxicological analysis performed on bones (the cranium and the ribs) in different states of preservation could provide to the forensic practitioner. Thirty cadavers with known pharmacological history, subjected to forensic autopsy at the Institute of Legal Medicine of Milan, were selected. Rib and cranium samples were collected from each body and separated into two parts in order to create two different states of preservation: One was cleaned from soft tissues and analyzed as a well-preserved bone sample; the other was submitted to a long maceration process, simulating complete skeletonization. All specimens were then processed with accelerated solvent extraction and the eluates analyzed using Q-Exactive™ Orbitrap™ Mass Spectrometer. The analysis of blood and skeletal matrices showed positive results for the tested substances in 63% of cases, mainly benzodiazepines, antidepressants, and drug abuse. Significant Pearson correlations were observed between non-macerated vs. macerated bone samples: r = 0.79 for rib samples, r = 0.61 for cranium samples, and r = 0.69 for all bone samples. As a consequence, the positive results confirm the potential of the bone tissue as an alternative matrix in forensic toxicology, even in cases of extremely decomposed bodies. This study also highlighted important elements for reconstructing the biological profile in cases of forensic anthropological concern.


Assuntos
Entorpecentes/análise , Preparações Farmacêuticas/análise , Costelas/química , Crânio/química , Detecção do Abuso de Substâncias/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Feminino , Toxicologia Forense/métodos , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Manejo de Espécimes
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