Cuphea is the largest genus of the Lythraceae family. It is popularly known as "sete-sangrias" in Brazil used in folk medicine as a diuretic, antipyretic, anti-inflammatory, laxative and ...antihypertensive agent. The raw material of Cuphea has shown promising results in the production of fitotherapics, which are chemically characterized by quercetin core flavonoids.
Present work aims to investigate the chemical composition of Cuphea calophylla, Cuphea carthagenensis, Cuphea glutinosa and Cuphea racemosa by UHPLC-MS using ESI-Q-TOF, and also to investigate the inhibition of angiotensin-converting enzyme (ACE) in vitro.
Leaves extraction was conducted by an ultrasound-assisted system under the following conditions: 40% ethanol, particle size ≤180 μm, plant:solvent ratio 1:20 (w/v) for 30 min. The leaf extracts were analyzed by UHPLC-MS positive mode ionization. For the inhibition of ACE, the leaf extracts used were obtained from different Cuphea species collected from several regions of Rio Grande do Sul (Brazil).
In total 26 polyphenolic compounds were proposed, which were mostly derived from quercetin, myricetin, and kaempferol. Of these compounds, ten are described in the genus for the first time. The ACE-inhibiting activities are presented in descending order: miquelianin (32.41%), C. glutinosa 1 (31.66%), C. glutinosa 5 (26.32%) and C. carthagenensis 1 (26.12%).
The obtained results suggest that the ACE-inhibiting potential may be increased by the interactions among the different phytoconstituents present in the crude extract. These results corroborate with the popular usage of Cuphea genus as diuretic and antihypertensive agents in folk medicine.
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•Inhibition of angiotensin I-converting enzyme and polyphenols composition of Cuphea spp.•Cuphea spp: Polyphenols composition and inhibition of angiotensin I-converting enzyme.•Study in vitro inhibitor ACE and polyphenols composition of Cuphea spp.•Polyphenols composition from leaves of Cuphea spp and inhibitor potential ACE.•Polyphenols from leaves of Cuphea spp and inhibition of angiotensin I-converting enzyme.
Cuphea glutinosa is a medicinal species abundant in South of Brazil, known because of its flavonoids, which have pharmacological properties as antioxidant, anti-hypertensive, diuretic, and ...antimicrobial. The present study aimed to optimize the extraction and validate an ultra-performance liquid chromatographic method coupled to a photodiode array detector (UPLC-PDA) method for the quantification of a chemical marker miquelianin in C. glutinosa leaves. The optimum conditions for the extraction of miquelianin from leaves of C. glutinosa were determined using a fractional factorial design (FFD) and a central composite design (CCD). An UPLC-PDA method was validated, following the ICH guidelines and RDC 166/2017 of ANVISA (Brazil). The extraction-optimization methodology was obtained with the following parameters: plant:solvent 1:60 (w/v), percentage solvent 38% ethanol, 60 min time, five extractions and particle size ≤ 180 μm. The validation parameters of the quantification method were satisfactory. The results revealed a method with excellent selectivity, linearity, precision (repeatability and intermediate precision were below 2.18 and 1.40%, respectively) and accuracy (mean recovery 90.6%). The average content of miquelianin was 1.03%. Briefly, the optimization of the extractive method in the leaves of C. glutinosa increased the concentration of miquelianin in the crude extract and the method was validated according to the current legislation.
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•Ultrasound-assisted extraction optimization and validation from Cuphea glutinosa.•Ultrasound extraction optimization and validation for miquelianin quantification.•Optimization and validation for the quantification of miquelianin in Cuphea glutinosa.•Optimization and validation for the quantification of miquelianin.
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•A simple direct infusion method by ESI-Q-TOF for quantification of meropenem in infusion fluids was validated.•Stability after reconstitution and degradation products in clinical use ...conditions.•Characterization of degradation products formed under different stress conditions.•Identification of a new degradation product formed in samples diluted in glucose 5%.
An ESI-MS/MS method through direct infusion was validated for quantitative analysis of meropenem powder for injection. The validation parameters were established in a rapid analysis of 30 s. Drug stability was studied through the submission to stress testing, resulting on four degradation products. Under hydrolytic conditions, in acid, neutral and alkaline media, the major degradation product was formed through the cleavage of the β-lactam ring. Oxidation of the drug using H2O2 (3%) showed the formation of two degradation products from a decarboxylation reaction and N-oxide formation. Under high humidity conditions, there was detected a dimer product. The stability of meropenem after reconstitution was studied in conditions that simulate its clinical use. In samples reconstituted and diluted in infusion fluids, an extensive degradation was observed. At room temperature meropenem maintained its content > 90% for up to 4 h when prepared in 5% glucose and for up to 12 h when prepared in 0.9% NaCl. Through ESI-MS/MS analyzes it was observed a degradation product formed by β-lactam ring cleavage, detected in all conditions studied. It was also identified a degradation product formed only in 5% glucose, generated by the hydrolysis of β-lactam followed by the attachment of a glucose molecule to the nitrogen of the pyrrolidine ring. In general, all the results obtained in the stability studies contribute to the knowledge about this antibiotic and future candidates of this class.
Sida tuberculata R. E. Fries (Malvaceae) is a pioneer species considered a weed in farm fields in Southern Brazil. Widely distributed in South Brazil, S. tuberculata is popularly used to treat ...inflammatory conditions.
The current study aimed to assess the in vitro cytotoxic and in vivo anti-inflammatory properties of S. tuberculata.
Initially, extracts obtained from leaves (STLE) and roots (STRE) were submitted to cytotoxicity tests using human leukocytes (non-malignant cell line) and HepG2 and MCF-7 (tumor cell lines). In sequence, anti-inflammatory properties were investigated against carrageenan-induced peritonitis model.
In vitro analyses displayed a significant decrease in human leukocytes viability without genotoxic damage. IC50 results from tumor cells presented significant decrease in cell viability, slightly more pronounced for STRE. In addition, STLE significantly inhibited the inflammatory and oxidative parameters (TBARS, NPSH, SOD, MPO activity, cell influx, and cytokines release).
Our findings indicate S. tuberculata extracts have cytotoxic potential more pronounced on tumor cell lines, as well as leaves extract shows a significant reduction in acute inflammation process, as already reported for Sida genus and specifically for this species.
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•Sida tuberculata, in vitro, cytotoxicity assay.•Sida tuberculata, in vivo, anti-inflammatory response.•Anti-inflammatory activities from Sida tuberculata leaves and roots extracts.
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 β‐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.
Posaconazole is a triazole antifungal drug approved by FDA in 2006. No bioassay is available in literature or official codes for potency determination in bulk.
To conduct an analytical study focused ...on posaconazole in bulk.
An alternative microbiological assay was validated for drug quantitation, applying agar diffusion technics (3 x 3 design), using Saccharomyces cerevisiae ATCC MYA 1942 as test microorganism (2% inoculum). An isocratic HPLC-DAD method, with C8 Shim-pack column (250 x 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 UPLC-QTOF-MS.
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. From 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), m/z 465 (DP3).
Microbiological method was adequately validated and demonstrated to be equivalent to physico-chemical ones. Impurities found are described for the first time in studies with posaconazole raw material.
a microbiological bioassay was developed for posaconazole; first-order kinetics was determined for photolytic degradation; structures for new degradation products were suggested.
Ceftaroline fosamil (prodrug) and ceftaroline (active form; degradation product) were simultaneously determined by a new stability-indicating HPLC method. These two forms were monitored during ...stability investigation of drug formulation reconstituted solution following the same conditions used for clinical use (refrigeration and room temperature). In general terms, ceftaroline fosamil is stable when stored at refrigerator until 48 h, with a drug residual content of 93.99% (in saline diluent) and 97.18% (in 5% glucose diluent). At room temperature, its chemical stability is critical, being necessary attention in the time infusion. Ceftaroline free basis was formed during stability testing, and its concentration has increased along the time. A forced degradation study was also performed for evaluation of the main degradation products, which were identified by LC-MS analysis. Applying selected stress conditions, five degradation products were structurally identified, with variation on side chain and cephalosporinic ring. The opened β-lactam ring and ceftaroline free basis can be highlighted.
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.
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.
By exploring the fragmentation data from mass spectrometry, the samples were classified using a chemometric model of partial least squares discriminant analysis (PLS-DA).
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.
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.
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.
Bauhinia forficata (BF) has been traditionally used as tea in folk medicine of Brazil for treatment of Diabetes mellitus (DM).
To evaluate the effects of BF leaf tea on markers of oxidative damage ...and antioxidant levels in an experimental model of hyperglycemia in human erythrocytes in vitro.
Human erythrocytes were incubated with high glucose concentrations or glucose and BF tea for 24h and 48h. After incubation lipid peroxidation and non-protein SH levels were analyzed. Moreover, quantification of polyphenols and flavonoids, iron chelating property, scavenging of DPPH, and prevention of lipid peroxidation in isolated lipids were also assessed.
A significant amount of polyphenols and flavonoids was observed. The main components found by LC-MS analysis were quercetin-3-O-(2-rhamnosyl) rutinoside, kaempferol-3-O-(2-rhamnosyl) rutinoside, quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside. BF tea presents important antioxidant and chelating properties. Moreover, BF tea was effective to increase non-protein SH levels and reduce lipid peroxidation induced by high glucose concentrations in human erythrocytes.
The antioxidant effects of BF tea could be related to the presence of different phenolic and flavonoids components. We believe that these components can be responsible to protect human erythrocytes exposed to high glucose concentrations against oxidative damage.
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