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•Edcysteroids were identified in infusions obtained from Sida tuberculata R.E. Fries.•Crude extracts exhibited in vitro anti-Candida krusei activity.•The leaves infusion was able to ...eradicate C. krusei biofilm in artificially CVC coupons.
Sida tuberculata is found in a region of South America and has traditionally been consumed as an infusion or tea. The chemical composition and antifungal activity of aqueous infusions from leaves and roots were investigated. LC–ESI-MS mass spectra were successfully obtained and used to identify four ecdysteroids: 20-hydroxyecdysone-3-O-β-d-glycopyranoside, 20-hydroxyecdysone, 20-hydroxyecdysone-3-O-β-d-xylose and a hydroxyecdysterone derivative. The in vitro antifungal activity was studied, and the minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) were established against Candida krusei isolates. The antibiofilm activity was evaluated by the determination of the biofilm removal efficiency in contaminated central venous catheter (CVC) coupons. The preparations exhibited antifungal activity against the species tested, with MICs ranging from 3.90 to 62.50μg/ml. The infusion removed the C. krusei biofilm after 90min of exposure. The observed bioactivity and composition of ecdysteroids will contribute to the future development of antifungal substances for clinical use or as food additives.
There is a growing interest in the pharmaceutical field concerning isoflavones topical delivery systems, especially with regard to their skin care properties and antiherpetic activity. In this ...context, the present work describes an ultra-fast liquid chromatography method (UFLC) for determining daidzein, glycitein, and genistein in different matrices during the development of topical systems containing isoflavone aglycones (IA) obtained from soybeans. The method showed to be specific, precise, accurate, and linear (0.1 to 5µgmL−1) for IA determination in soybean acid extract, IA-rich fraction obtained after the purification process, IA loaded-nanoemulsions, and topical hydrogel, as well as for permeation/retention assays in porcine skin and porcine esophageal mucosa. The matrix effect was determined for all complex matrices, demonstrating low effect during the analysis. The stability indicating UFLC method was verified by submitting IA to acidic, alkaline, oxidative, and thermal stress conditions, and no interference of degradation products was detected during analysis. Mass spectrometry was performed to show the main compounds produced after acid hydrolysis of soybeans, as well as suggest the main degradation products formed after stress conditions. Besides the IA, hydroxymethylfurfural and ethoxymethylfurfural were produced and identified after acid hydrolysis of the soybean extract and well separated by the UFLC method. The method’s robustness was confirmed using the Plackett-Burman experimental design. Therefore, the new method affords fast IA analysis during routine processes, extract purification, products development, and bioanalytical assays.
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•An analytical and bioanalytical UFLC method for isoflavone aglycones was validated.•Acid hydrolysis of soybeans was performed to obtain the isoflavone aglycones.•Extract impurities as hydroxymethylfurfural and ethoxymethylfurfural were detected.•A pure rich-fraction was produced and incorporated in nanoemulsions and hydrogels.•Permeation assays in porcine skin or porcine esophageal mucosa were performed.
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 UHPLC–MS. The in vivo antinociceptive potential of STLE (10–300 mg kg−1) was assessed in mice subjected to the acetic acid‐induced 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 20‐hydoxyecdysone (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 formalin‐induced 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 μ‐opioid receptor. Thus, the results suggest the existence of antinociceptive potential from S. tuberculata extracts being in accordance to the traditional use.
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.
Bauhinia forficata is used in folk medicine for its hypoglycemiant effect. In the south of Brazil, the subspecies pruinosa is found in a region with the characteristic flora, pampa biome. This ...species has been consumed by the local population as a tea for diabetes treatment. We studied the chemical composition of hydroethanolic extracts using LC/ESI-MS. The leaf extracts were prepared by percolation with 50% (v/v) ethanol. The chromatographic analyses were performed using a reverse-phase system, gradient elution with acetonitrile:phosphoric acid 0.05%, and ESI-MS in the positive ion mode. The chemical profile of the flavonoids was suggested to involve four quercetin and kaempferol glycosides.
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.
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 (H2O2 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.
Powder mixing is an important operation routinely used in many industries, including pharmaceuticals. The quality of products depends on certain operating conditions, such as the equipment, technical ...parameters and formulation. In this work, an operational qualification of powder mixing during large scale production in a pharmaceutical industry was performed. A simple and practical protocol was followed. Using a V-blender and dry powder mixing, the operation was tested to illustrate the effect of mixing time on the homogeneity of the drug in the mixture, demonstrating that this parameter can be used as a secure parameter to control this pharmaceutical operation on a large scale during batch production and using an off-line monitoring technique.
Powder mixing operation was evaluated by an off-line monitoring technique during routine production in the pharmaceutical industry. These tests were performed considering regulatory requirements and the process validation procedure.
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A high-performance liquid chromatographic method and a UV spectrophotometric method for the quantitative determination of meropenem, a highly active carbapenem antibiotic, in powder for injection ...were developed in present work. The parameters linearity, precision, accuracy, specificity, robustness, limit of detection and limit of quantitation were studied according to International Conference on Harmonization guidelines. Chromatography was carried out by reversed-phase technique on an RP-18 column with a mobile phase composed of 30 mM monobasic phosphate buffer and acetonitrile (90:10; v/v), adjusted to pH 3.0 with orthophosphoric acid. The UV spectrophotometric method was performed at 298 nm. The samples were prepared in water and the stability of meropenem in aqueous solution at 4 and 25
°C was studied. The results were satisfactory with good stability after 24 h at 4
°C. Statistical analysis by Student's
t-test showed no significant difference between the results obtained by the two methods. The proposed methods are highly sensitive, precise and accurate and can be used for the reliable quantitation of meropenem in pharmaceutical dosage form.
The stability of broad-spectrum antibiotic meropenem was studied in order to investigate the kinetics of degradation of this drug in powder for injection and reconstituted sample. Carbapenem was ...submitted to conditions of accelerated thermal decomposition. Degradation of meropenem was adequately modeled by specific equations for order rate kinetics. The analyses of the degraded samples were performed by high-performance liquid chromatographic (HPLC) method and microbiological assay. At higher temperatures, the decomposition reactions of meropenem in powder for injection could be described by first-order kinetics. The higher rate of degradation was observed in meropenem reconstituted in 0.9% sodium chloride, and the thermal decomposition obeyed also first-order kinetics. The results obtained confirm the reliability of chromatographic method for determining the kinetics run of meropenem in the presence of its degradation products. The present study reveals the thermal lability of the drug, especially as reconstituted sample. Thus, appropriate thermal protection is recommended during the storage and handling.
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