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1.
Biomed Chromatogr ; 38(10): e5971, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39079937

RESUMEN

Drug biotransformation studies emerges as an alternative to pharmacological investigations of metabolites, development of new drug candidates with reduced investment and most efficient production. The present study aims to evaluate the capacity of biotransformation of rifampicin by the filamentous fungus Aspergillus niger ATCC 9029. After incubation for 312 h, the drug was metabolized to two molecules: an isomer (m/z 455) and the rifampicin quinone (m/z 821). The monitoring of metabolite formation was performed by high-performance liquid chromatography, followed by their identification through ultra-high-performance liquid chromatography coupled to tandem mass spectrometer. In vitro antimicrobial activity of the proposed metabolites was evaluated against Staphylococus aureus microorganism, resulting in the loss of inhibitory activity when compared with the standards, with minimum inhibitory concentration of 7.5 µg/ml. The significant biotransformation power of the ATCC 9029 strain of A. niger was confirmed in this study, making this strain a candidate for pilot studies in fermentation tanks for the enzymatic metabolization of the antimicrobial rifampicin. The unprecedented result allows us to conclude that the prospect of new biotransforming strains in species of anemophilic fungi is a promising choice.


Asunto(s)
Aspergillus niger , Biotransformación , Pruebas de Sensibilidad Microbiana , Rifampin , Espectrometría de Masas en Tándem , Aspergillus niger/metabolismo , Aspergillus niger/efectos de los fármacos , Rifampin/farmacología , Rifampin/metabolismo , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas en Tándem/métodos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/metabolismo , Antiinfecciosos/farmacología , Antiinfecciosos/metabolismo , Antiinfecciosos/química
2.
Artículo en Inglés | MEDLINE | ID: mdl-38213844

RESUMEN

Natural compounds that have the potential to act as antimicrobials and antitumors are a constant search in the field of pharmacotherapy. Eragrostis plana NEES (Poaceae) is a grass with high allelopathic potential. Allelopathy is associated with compounds generated in the primary and secondary metabolism of the plant, which act to protect it from phytopathogens. Tabernaemontana catharinensis A DC (Apocynaceae), a tree in which its leaves and bark are used for the preparation of extracts and infusions that have anti-inflammatory and antinociceptive effects, is attributed to its phytochemical constitution. The objective of this study was to elucidate the phytochemical constitution, the antibacterial potential, the toxicity against immune system cells, hemolytic potential, and antitumor effect of methanolic extracts of E. plana and T. catharinensis. The phytochemical investigation was carried out using the UHPLC-QTOF MS equipment. The antibacterial activity was tested using the broth microdilution plate assay, against Gram-negative and Gram-positive strains, and cytotoxicity assays were performed on human peripheral blood mononuclear cells (PBMC) and in vitro hemolysis. Antitumor activity was performed against the colon cancer cell line (CT26). Results were expressed as mean and standard deviation and analyzed by ANOVA. p < 0.05 was considered significant. More than 19 possible phytochemical constituents were identified for each plant, with emphasis on phenolic compounds (acids: vanillic, caffeic, and quinic) and alkaloids (alstovenine, rhyncophylline, amezepine, voacangine, and coronaridine). Both extracts showed antibacterial activity at concentrations below 500 µg/mL and were able to decrease the viability of CT26 at concentrations below 2000 µg/mL, without showing cytotoxic effect on PBMCs and in vitro hemolysis at the highest concentration tested. This is the first report of the activity of E. plana and T. catharinensis extracts against colon cancer cell line (CT26). Studies should be carried out to verify possible molecular targets involved in the antitumor effect in vivo.

4.
J AOAC Int ; 105(3): 915-927, 2022 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-34935936

RESUMEN

BACKGROUND: The analysis of plant material from Cannabis sativa L. has long been targeted on its main psychologically active metabolite, Δ9-tetrahydrocannabinol (THC). In addition to the diverse plant composition and medicinal interest in several cannabinoids, these compounds may also be related to the different characteristics of samples sold illegally. Currently, it is indisputable that other cannabinoids should also be considered in cannabis assays. Mass spectrometry has been used to identify and characterize substances in the most different scenarios, and knowing the analyte fragmentation profile is essential for characterizing samples of diverse origin. OBJECTIVE: In this work, flow injection analysis-tandem mass spectrometry with electrospray ionization (FIA-ESI-MS/MS) in positive and negative modes was used to evaluate the fragmentation profiles of eight cannabinoids commonly found in cannabis samples: THC, tetrahydrocannabinolic acid, Δ8-tetrahydrocannabinol, cannabidiol, cannabidiolic acid, cannabigerol, cannabigerolic acid and cannabinol. METHODS: By exploring the fragmentation data from mass spectrometry, the samples were classified using a chemometric model of partial least squares discriminant analysis (PLS-DA). RESULTS: When ESI in negative mode is used with adequate collision energies, it is possible to identify differences in the fragmentation of isomers. Based on that, chemometric tools were employed to classify different samples. The PLS-DA applied to FIA-ESI-MS/MS data yielded satisfactory classification. CONCLUSION: Thus, the results presented can be applied as a preliminary tool in the analysis of unknown samples, guiding more accurate investigations in terms of chemical composition. HIGHLIGHTS: This study of the cannabinoid fragmentation pattern by flow injection MS showed that cannabinoids can be distinguished by their fragmentation spectra after negative electrospray ionization. Multivariate data analysis (PLS-DA) allowed classification of different cannabis samples.


Asunto(s)
Cannabinoides , Cannabis , Alucinógenos , Cannabinoides/análisis , Cannabis/química , Dronabinol/análisis , Análisis de Inyección de Flujo , Espectrometría de Masas en Tándem/métodos
5.
Chem Biodivers ; 18(7): e2100041, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34000101

RESUMEN

The present study investigates the chemical composition, anti-inflammatory, and antihypertensive activities, in vitro, from extracts of Cuphea lindmaniana and Cuphea urbaniana leaves. The extraction was performed ultrasound-assisted, and UHPLC/MS analysis was in positive mode ionization. The anti-inflammatory activity of the extracts and miquelianin were assayed at concentrations 0.001-10 µg/mL by chemotaxis on rat polymorphonuclear neutrophils. The antihypertensive activity was performed by angiotensin-converting enzyme (ACE) inhibition. From the nineteen proposed compounds, six of them are described for the first time in this genus. The extracts displayed antichemotactic effect with a reduction of 100 % of the neutrophil migration, in vitro, in most concentrations. The ACE-inhibition presented results ranging from 19.58 to 22.82 %. In conclusion, C. lindmaniana and C. urbaniana extracts contain a rich diversity of flavonoids and display in vitro anti-inflammatory and antihypertensive potential. Thus, this study could serve as a scientific baseline for further investigation, on developmental novel products with therapeutic actions.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antiinflamatorios/farmacología , Antihipertensivos/farmacología , Cuphea/química , Neutrófilos/efectos de los fármacos , Extractos Vegetales/farmacología , Polifenoles/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/aislamiento & purificación , Angiotensinas/antagonistas & inhibidores , Angiotensinas/metabolismo , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antihipertensivos/química , Antihipertensivos/aislamiento & purificación , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Polifenoles/química , Polifenoles/aislamiento & purificación , Ratas
6.
J AOAC Int ; 104(4): 1055-1064, 2021 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-33470411

RESUMEN

BACKGROUND: Posaconazole is a triazole antifungal drug that was approved by the U.S. Food and Drug Administration in 2006. No bioassay of it is available in the literature nor official codes for potency determination in bulk. OBJECTIVE: To conduct an analytical study focused on posaconazole in bulk. METHODS: An alternative microbiological assay was validated for drug quantitation, applying agar diffusion technics (3 × 3 design), using Saccharomyces cerevisiae ATCC MYA 1942 as a test microorganism (2% inoculum). An isocratic HPLC-DAD method, with C8 Shim-pack column (250 × 4.6 mm, 5 µm) and methanol-water (75:25 v/v) mobile phase was used for stress stability by photolysis and oxidation, indicating the formation of degradation products, which were investigated by ultra-performance liquid chromatography to quadrupole time-of-flight mass spectrometry. RESULTS: The established conditions for the bioassay were satisfactory. It was linear in the range evaluated (2.5-10.0 µg/mL), as well as precise, accurate, and robust. Stress tests showed drug susceptibility to the factors evaluated (60% of degradation after 120 min). Kinetics curves for photolytic decomposition followed first-order kinetics. From a photolytic and oxidative degraded matrix, three major degradation products were identified as being derivatives with modifications in the piperazine central ring and in the triazole and triazolone side chains, whose mass spectra results were m/z 683 (DP1), m/z 411 (DP2), and m/z 465 (DP3). CONCLUSIONS: The microbiological method was adequately validated and demonstrated to be equivalent to physico-chemical ones. The impurities found are described for the first time in studies with posaconazole raw material. HIGHLIGHTS: A microbiological bioassay was developed for posaconazole, first-order kinetics was determined for photolytic degradation, and structures for new degradation products were suggested.


Asunto(s)
Antifúngicos , Bioensayo , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Estabilidad de Medicamentos , Cinética , Espectrometría de Masas , Triazoles
7.
Nat Prod Res ; 35(24): 6058-6061, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32911965

RESUMEN

Cuphea genus (Lythraceae) popularly known in Brazil as "sete-sangrias", it's described as antimicrobial, anti-inflammatory, diuretic and antihypertensive mainly. Investigating the chemotactic ability plays an important role in the identification of new anti-inflammatory agents. Thus, this research aims to assay the antichemotactic activity of hydroethanolic extracts of C. calophylla, C. carthagenensis, C. glutinosa, and C. racemosa as well as the compounds miquelianin and myricitrin. The antichemotactic activity of the hydroethanolic extracts, miquelianin, and myricitrin were assayed at concentrations 0.001 to 10 µg/mL in the lipopolysaccharide-induced chemotaxis on rat polymorphonuclear neutrophils. All the assayed samples displayed antichemotactic activity with reduction of the neutrophil migration in the range of 4.46-100%, and an IC50 value in the range of 0.30-1.24 µg/mL. Thus, this study demonstrates that the extracts hydroethanolic of Cuphea species, miquelianin, and myricitrin display a significant antichemotactic activity. Therefore, in future studies, extracts from Cuphea spp. could be used as anti-inflammatory drugs.


Asunto(s)
Cuphea , Animales , Antiinflamatorios/farmacología , Antihipertensivos , Lipopolisacáridos , Extractos Vegetales/farmacología , Ratas
8.
Braz. J. Pharm. Sci. (Online) ; 57: e18896, 2021. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1339309

RESUMEN

Tizanidine hydrochloride is a centrally acting skeletal muscle relaxant, used in the management of spasticity. This drug is commercially available only as tablets, which highlights the need to develop oral liquid formulations. In the hospital environment, this aspect is circumvented by the preparation of suspensions, to allow administration to children and adults with impaired swallowing, but there are no data regarding their stability. The purpose of this study was to evaluate the physicochemical andmicrobiological stability of liquid dosage forms prepared in the hospital environment from tizanidine hydrochloride tablets, applying high performance liquid chromatography (HPLC) and microbiological analysis. A simple and stability-indicating HPLC method was developed and validated for specificity, linearity, limits of detection and quantification, precision, accuracy and robustness. The liquid formulations were placed in amber PET and glass bottles, which were stored under three different conditions: at room temperature, under refrigeration and at 40 ºC. The liquid formulations were analyzed and demonstrated chemical stability for 56 days, allowing their use for long periods. However, the determination of microbiological stability showed that these formulations are prone to microbial contamination, which has dramatically reduced its stability to 7 days, in both bottles and at all evaluated temperatures


Asunto(s)
Comprimidos/farmacología , Preparaciones Farmacéuticas/análisis , Técnicas Microbiológicas/instrumentación , Cromatografía Líquida de Alta Presión/métodos , Sensibilidad y Especificidad , Ámbar , Formas de Dosificación , Estabilidad de Medicamentos , Métodos
9.
J Tradit Complement Med ; 9(4): 383-392, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31453135

RESUMEN

The production of reactive species over physiological levels associated to pathogenic bacteria could represent a high risk for many diseases. The Rosmarinus officinalis L. is used around the world due its pharmacological proprieties. So, in this study our aim is to test for the first time if R. officinalis L. extract (eeRo) and its fractions (DCM, EA, ButOH) could have better or similar antioxidant action to standars and among themselves in vitro or ex vivo, in brain, stomach and liver of rats. Moreover, we intend to clarify their possible effects on pathogenic bacteria. The eeRo was obtained from the dried leaves subjected to an alcoholic extraction and fractioned. The quantification of the constituents of eeRo and fractions were done by HPLC. The antioxidant proprieties of R. officinalis was analyzed by DPPH•- radical scavenging, total antioxidant, dichlorofluorescein, lipid peroxidation and sodium nitroprusside -induced lipid peroxidation assays. The Minimum inhibitory concentrations of R. officinalis L. were tested with standard strains of danger bacteria. The eeRo, DCM, EA had significant total antioxidant and DPPH•- radical scavenging activities. The DCM and eeRo got significant effects against basal levels of reactive species in liver, stomach and brain. The eeRo and DCM protected the liver and brain against lipid peroxidation. The eeRo, DCM, EA and ButOH had inhibitory effect in the Gram-positive and Gram-negative bacteria. In general way, the DCM and eeRo had the best antioxidant and antibacterial effects among all tested fractions.

10.
Biomed Chromatogr ; 33(6): e4496, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30663135

RESUMEN

The purpose of this paper is to describe the glycosylation of ambrisentan (AMB) by cultures of Cunninghamella elegans ATCC 9245. AMB is an endothelin receptor antagonist, which is used to treat pulmonary arterial hypertension. Filamentous fungi are morphologically complex and may exhibit different forms depending on the species and the nature of the culture medium. A biotransformation study was conducted to investigate the ability of C. elegans to metabolize AMB. Parameters were optimized by testing on different culture media and concentrations, pH, drug concentration, static and shaking conditions. Ambrisentan's metabolite, obtained after 240 h of incubation as a result of glycosylation pathway, was separated by HPLC and determined by high-resolution mass spectrometry. The method showed linearity over 300-1000 µg mL-1 (r = 0.998). Accuracy, precision, robustness and stability studies agree with international guidelines. Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and used little solvent.


Asunto(s)
Cunninghamella/metabolismo , Glicósidos/análisis , Glicósidos/metabolismo , Fenilpropionatos/análisis , Fenilpropionatos/metabolismo , Piridazinas/análisis , Piridazinas/metabolismo , Biotransformación , Técnicas de Cultivo de Célula , Cromatografía Líquida de Alta Presión , Glicósidos/química , Espectrometría de Masas , Fenilpropionatos/química , Piridazinas/química
11.
Phytother Res ; 33(1): 224-233, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30375066

RESUMEN

Sida tuberculata R.E.Fr. (Malvaceae) is a medicinal plant widely found in Southern Brazil, and popularly used for inflammatory disorders and to pain relief. A phytochemical analysis followed by an investigation about antinociceptive potential and mechanism of action were performed with leaves and roots extracts. Methanolic extracts, designated as S. tuberculata leaves extract (STLE) and S. tuberculata roots extract, were analyzed both by UHPLC­MS. The in vivo antinociceptive potential of STLE (10­300 mg kg−1) was assessed in mice subjected to the acetic acid­induced abdominal writhes and formalin model. Agonist/antagonist tests and computational docking suggest the involvement of opioid and adenosinergic systems. The main chemical class detected on extracts was the ecdysteroids, and 20­hydoxyecdysone (20HE) was confirmed as the major phytoconstituent. The pretreatment with STLE (100 mg kg−1) reduced more than 70% abdominal contortions induced by acetic acid model and produced significant inhibition on formalin­induced licking response. The mechanism of action study revealed STLE might act through opioid and adenosine systems. Molecular docking suggested kaempferol derivative and 20HE might interacting with µ­opioid receptor. Thus, the results suggest the existence of antinociceptive potential from S. tuberculata extracts being in accordance to the traditional use.


Asunto(s)
Analgésicos/farmacología , Malvaceae/química , Simulación del Acoplamiento Molecular , Nocicepción , Extractos Vegetales/farmacología , Ácido Acético , Animales , Conducta Animal , Brasil , Formaldehído , Masculino , Metanol , Ratones , Dolor/inducido químicamente , Fitoquímicos/farmacología , Hojas de la Planta/química , Raíces de Plantas/química , Plantas Medicinales/química
12.
Biomed Chromatogr ; 33(4): e4471, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30549056

RESUMEN

Carbapenems show recognized instability in aqueous solutions; therefore some care must be taken in their handling and preparation and their use in the hospital environment. The stability and degradation products of imipenem were investigated from conditions that simulate its clinical use. For this, a simple stability-indicating method by HPLC-DAD was validated with a focus on the quantitation of drug concentration remaining from infusion solutions (sodium chloride 0.9% and glucose 5%). The degradation products formed were identified by high-resolution mass spectrometry (ESI-Q-TOF-MS/MS), with detection of the [M + H]+ ions at m/z 318 (DP-1), m/z 599 (DP-2) and m/z 658 (DP-3). The most probable elemental compositions were obtained with a high degree of confidence, where the error between the masses observed and calculated was 1.25 ppm for DP-1, -0.33 ppm for DP-2 and 1.82 ppm for DP-3. The DP-1 degradation product resulted from cleavage of the ß-lactam ring; DP-2 corresponded to the drug dimer; and DP-3 was generated from the interaction between imipenem and cilastatin. The proposed method provides a safe and reliable alternative for the quantitation of imipenem, and the stability data obtained by ESI-Q-TOF help in understanding the drug behavior under the conditions of clinical use.


Asunto(s)
Imipenem/análisis , Imipenem/química , Espectrometría de Masas/métodos , Cromatografía Líquida de Alta Presión , Contaminación de Medicamentos , Estabilidad de Medicamentos , Imipenem/normas , Modelos Lineales , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
13.
Oxid Med Cell Longev ; 2018: 5758191, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30228856

RESUMEN

Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 ß-HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.


Asunto(s)
Ciclofosfamida/efectos adversos , Sustancias Protectoras/farmacología , Reproducción/efectos de los fármacos , Tribulus/química , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Sulfato de Deshidroepiandrosterona/metabolismo , Diosgenina/análogos & derivados , Diosgenina/análisis , Masculino , Ratones , Extractos Vegetales/farmacología , Estándares de Referencia , Saponinas/análisis , Semen/metabolismo , Túbulos Seminíferos/efectos de los fármacos , Túbulos Seminíferos/patología , Espermatozoides/efectos de los fármacos , Espermatozoides/metabolismo , Testosterona/sangre
14.
Biomed Chromatogr ; 32(11): e4348, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30047558

RESUMEN

The antipsychotic paliperidone was investigated with a focus on stability, degradation impurities and kinetics reaction profile. Osmotic tablets 3 mg (OROS® ) were subjected to extraction in an ultrasonic bath and the resulting acidic solution was stressed by forced conditions. Degraded samples were monitored by HPLC-DAD in different storage times for acidic and alkaline hydrolysis, oxidation, heat and photolysis. Photolysis was shown to be a strong degradation factor, with a drug content of 24.64% remaining after 24 h. Oxidation (H2 O2 18%) caused a slow decomposition, with a drug content of 83.49% remaining after 72 h. Through kinetics graphics, first-order reactions were found for oxidation, heat and photolysis. By UPLC-MS analysis, the degraded matrix could be investigated for identification of impurities with m/z 445.3128, m/z 380.8906, m/z 364.9391, m/z 232.9832 and m/z 217.0076, allowing the identification of derivatives N-oxide and with modifications in the lactam, benzisoxazole and pyrimidine rings. Paliperidone in liquid state, like analytical solutions or formulation, must be carefully handled to avoid drug exposure, specially in storage conditions.


Asunto(s)
Palmitato de Paliperidona/análisis , Palmitato de Paliperidona/química , Cromatografía Líquida de Alta Presión/métodos , Estabilidad de Medicamentos , Cinética , Espectrometría de Masas , Oxidación-Reducción , Fotólisis , Comprimidos
15.
Artículo en Inglés | MEDLINE | ID: mdl-28584558

RESUMEN

Campomanesia xanthocarpa is known in Brazil as Guabiroba and is popularly used for various diseases, such as inflammatory, renal, and digestive diseases and dyslipidemia. The aim of the study was to analyze the chemical composition and investigate the effects of aqueous extract of C. xanthocarpa on the blood pressure of normotensive rats, analyzing the possible action mechanism using experimental and in silico procedures. The extract was evaluated for total phenolic compounds and total flavonoid content. The chemical components were determined by HPLC analyses. Systolic and diastolic blood pressure and heart rate were measured with extract and drugs administration. The leaves of C. xanthocarpa presented the relevant content of phenolics and flavonoids, and we suggested the presence of chlorogenic acid, gallic acid, quercetin, and theobromine. The acute administration of aqueous extract of C. xanthocarpa has a dose-dependent hypotensive effect in normotensive rats, suggesting that the action mechanism may be mediated through the renin-angiotensin system by AT1 receptor blockade and sympathetic autonomic response. Docking studies showed models that indicated an interaction between chlorogenic acid and quercetin with the AT1 receptor (AT1R) active site. The findings of these docking studies suggest the potential of C. xanthocarpa constituents for use as preventive agents for blood pressure.

16.
Biomed Chromatogr ; 31(8)2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28135762

RESUMEN

A ultra-fast liquid chromatography method applied to quantitation of doripenem in powder for injection was validated. Validation parameters were assayed and a rapid analysis was established by a reversed-phase system comprising a C18 column endcapped (50 × 4.0 mm, 2.0 µm), mobile phase consisting of phosphoric acid 0.01% (pH 3.8) and acetonitrile (98:02, v/v) and a flow rate of 0.4 mL min-1 . Drug stability was studied through submission to forced conditions, allowing the major degradation products to be detected and the kinetics parameters to be established. Thermal and oxidative degradation were determined, and indicated a kinetic decomposition following first and second order, respectively. The main degradation products were identified by LC-MS analysis, and the results were evaluated in order to suggest the chemical structures corresponding to respective masses and fragmentations. Six compounds were identified, with m/z 411, 427, 437, 634, 650 and 664. All of them resulted from cleavage of ß-lactam ring and alcoholic chain and/or dimerization. These experimental results provide valuable information about the stability of doripenem reconstituted solution and procedures for its handling and storage.


Asunto(s)
Antibacterianos/química , Carbapenémicos/química , Cromatografía Líquida de Alta Presión , Doripenem , Estabilidad de Medicamentos , Calor , Cinética , Oxidación-Reducción , Espectrometría de Masa por Ionización de Electrospray
17.
Environ Toxicol ; 32(1): 188-196, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26663770

RESUMEN

Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 ß-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017.


Asunto(s)
Arándanos Azules (Planta)/química , Intoxicación por Cadmio/tratamiento farmacológico , Enfermedades del Ovario/inducido químicamente , Enfermedades del Ovario/tratamiento farmacológico , Extractos Vegetales/farmacología , Porfobilinógeno Sintasa/metabolismo , 11-beta-Hidroxiesteroide Deshidrogenasas/metabolismo , Animales , Intoxicación por Cadmio/patología , Femenino , Glutatión Peroxidasa/metabolismo , Glutatión Sintasa/metabolismo , Ratones , Enfermedades del Ovario/patología , Folículo Ovárico/efectos de los fármacos , Porfobilinógeno Sintasa/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
18.
Food Chem ; 209: 185-95, 2016 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-27173551

RESUMEN

Chimarrão or mate is a popular beverage from South America that is drank with successive infusions. Although yerba mate extracts have been widely studied, few studies have described the extract contents in beverages. Using yerba mate samples from Brazil, Argentina, and Uruguay, we examined the extract chromatographic profiles, total polyphenol content and their capacities to chelate iron. In addition, we analyzed antioxidant activity by examining the ability of the extracts to scavenge DPPH and NO. Our results showed that the amount of extracted compound was highest in yerba mate extract from Uruguay, followed by Argentina, then Brazil. Herbs from all three areas had a significant capacity to inhibit DPPH and NO free radicals. The Brazilian and Uruguayan herbs had an 80% iron chelation capacity (p<0.001), while the iron chelation capacity of the Argentinean herb was lower but still significant (p⩽0.05). We conclude that the compound concentration decreases with successive extractions, while the antioxidant capacity is maintained at significant levels.


Asunto(s)
Bebidas/análisis , Quelantes/química , Manipulación de Alimentos/métodos , Depuradores de Radicales Libres/química , Depuradores de Radicales Libres/aislamiento & purificación , Hierro/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Argentina , Brasil , Quelantes/aislamiento & purificación , Radicales Libres/análisis , Ilex paraguariensis/química , Polifenoles/química , Polifenoles/aislamiento & purificación
19.
Oxid Med Cell Longev ; 2016: 8902954, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26839634

RESUMEN

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.


Asunto(s)
Bauhinia/química , Diabetes Mellitus Experimental/patología , Hígado/patología , Estrés Oxidativo , Tés de Hierbas , Animales , Glucemia/metabolismo , Western Blotting , Peso Corporal/efectos de los fármacos , Catalasa/metabolismo , Cromatografía Líquida de Alta Presión , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/enzimología , Proteínas HSP70 de Choque Térmico , Hígado/efectos de los fármacos , Ratones , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Tamaño de los Órganos/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Porfobilinógeno Sintasa/metabolismo , Superóxido Dismutasa/metabolismo , Tés de Hierbas/toxicidad , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
20.
Rev. ciênc. farm. básica apl ; Rev. ciênc. farm. básica apl;36(4): 491-495, 01/10/2015.
Artículo en Inglés | LILACS | ID: biblio-2583

RESUMEN

The aim of this work was to develop a simple, fast and reproducible spectrophotometric method for the analysis of posaconazole in raw material. The established conditions were: methanol as extracting solvent, detection wavelength of 260 nm, Shimadzu double beam spectrophotometer 1800 model with 1 cm quartz cells. Linearity was demonstrated in the concentration range of 5.0 a 25.0 µg/mL (r = 0.9999). Reproducibility and intermediate precision were confirmed by low RSD values (0.49 to 0.82%). Accuracy, evaluated through recovery test, was adequate, with 98.20% of mean recovery. Specificity and robustness were also demonstrated. The mean amount found for samples was 100.82%. The proposed method was considered suitable for the intended purpose, mainly in routine analysis of quality control laboratories. When compared to the previously developed HPLC, no statistical difference was observed, what made the UV spectrophotometric method a reliable alternative.


O objetivo deste trabalho foi desenvolver um método espectrofotométrico simples, rápido e reprodutível para a análise de posaconazol na matéria-prima. As condições estabelecidas foram: metanol como solvente extrator, comprimento de onda de 260 nm e espectrofotômetro de duplo feixe Shimadzu, modelo 1800, com cubetas de quartzo de 1 cm. A linearidade foi demonstrada na faixa de concentração de 5,0 a 25,0 µg/mL (r = 0,9999). A reprodutibilidade e a precisão intermediária foram confirmadas pelos baixos valores de desvio padrão relativo (0,49 a 0,82%). A exatidão, avaliada pelo teste de recuperação, foi adequada, com recuperação média de 98,20%. A especificidade e a robustez também foram demonstradas. O teor médio encontrado nas amostras foi de 100,82%. O método proposto foi considerado adequado, principalmente para a análise de rotina em laboratórios de controle de qualidade. Quando comparado com o método por HPLC, não houve diferença estatística, o que torna o método por espectrofotometria UV uma alternativa segura.


Asunto(s)
Antifúngicos/análisis , Triazoles/análisis , Cromatografía Líquida de Alta Presión/métodos , Control de Calidad , Espectrofotometría/métodos
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