Phentolamine bioequivalence study

Objective: To assess the bioequivalence of 2 tablet formulations of phentolamine (Regitine phentolamine 40 mg tablet formulation by Novartis, Brazil, as test formulation, and Vasomax, phentolamine 40 mg tablet formulation by Schering Plough S.A., Brazil, as reference formulation). Methods: A single 40 mg oral dose of each formulation was administered to 36 male healthy volunteers. The study was conducted after screening, using an open, randomized, 2-period crossover design, a 7-day interval between doses, and wash-out period of at least 4 weeks. Plasma samples for determination of phentolarnine were obtained predose and at intervals over 720 min postdose. Plasma concentrations were quantified by reversed-phase liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray ionization using multiple reactions monitoring (MRM) method. Precision of the method was evaluated using calibration curves and plasma quality control samples. The subjects were monitored throughout the study. Systolic and diastolic blood pressure and pulse rate measurement were taken predose and at intervals up to 720 min. Tolerance of both products was good. No serious adverse reactions were reported. The pharmacokinetic parameters calculated for both compounds included: AUC((0-720 min)), AUC((0-infinity)), C-max,C- C-max/AUC((0-720 min),) t(max), t(1/2) and k(c). Results: the maximum concentrations reached (Cmax) were compared. Regitine 40 mg formulation C-max geometric mean ratio was 108.29% (90% Cl = 98.58 - 118.96) of Vasomax 40 mg formulation. The areas under the curve (AUC((0-720 min))) were compared. Regitine 40 formulation (AUC((0-720 min)) geometric mean ratio was 102.33% (90% Cl = 97.21 - 107.72) of Vasomax 40 mg formulation. Conclusion: Since the 90% Cl for both Cmax and AUC ratio where inside the 80 to 125% interval proposed by the Food and Drug Administration, it is concluded that Regitine 40 mg tablet is bioequivalent to Vasomax for the rate and extent of absorption.

Contaminação por herbicidas em corpos hídricos da microbacia do Córrego Rico (SP) e aspectos toxicológicos de atrazine a juvenis de Piaractus mesopotamicus

Pós-graduação em Agronomia (Produção Vegetal) - FCAV

Avaliação da degradação fotoquímica de corante alimentício e lixiviação de corantes têxteis de fibras de algodão expostos a suor sintético por método cromatográficos

Pós-graduação em Química - IQ

Fat-Soluble Bioactive Components in Colored Rice Varieties

Bioactive components in rice vary depending on the variety and growing condition. Fat-soluble components such as gamma-oryzanol, tocopherols, tocotrienols, carotenoids, and fatty acids were analyzed in brown, sugary brown, red, and black rice varieties using established high-performance liquid chromatography (HPLC) and GC methodologies. In addition, these colored rice varieties were further analyzed using a high-resolution liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) (LTQ-Orbitrap XL) to identify the [M-H](-) ions of gamma-oryzanol, ranging from m/z 573.3949 to 617.4211. The highest content of tocopherols (alpha-, 1.5; gamma-, 0.5 mg/100 g) and carotenoids (lutein 244; trans-beta carotene 25 mu g/100 g) were observed in black rice; tocotrienols (alpha-, 0.07; gamma-, 0.14 mg/100 g) in red rice, and gamma-oryzanol (115 mg/100 g) in sugary brown rice. In all colored rice varieties, the major fatty acids were palmitic (16:0), oleic (18:1n-9), and linoleic (18:2n-6) acids. When the gamma-oryzanol components were further analyzed by LC-MS/MS, 3, 10, 8, and 8 triterpene alcohols or sterol ferulates were identified in brown, sugary brown, red, and black rice varieties, respectively. Such structural identification can lead to the elucidation of biological function of each component at the molecular level. Consumption of colored rice rich in beneficial bioactive compounds may be a useful dietary strategy for achieving optimal health.

Determination of anticonvulsants in human plasma using SPME in a heated interface coupled online to liquid chromatography (SPME-LC)

A simple and sensitive method using solid phase microextraction (SPME) and liquid chromatography (LC) with heated online desorption (SPME-LC) was developed and validated to analyze anticonvulsants (AEDs) in human plasma samples. A heated lab-made interface chamber was used in the desorption procedure, which allowed the transference of the whole extracted sample. The SPME conditions were optimized by applying an experimental design. Important factors are discussed such as fiber coating types, pH, extraction time and desorption conditions. The drugs were analyzed by LC, using a C18 column (150 mm 4.6 mm 5 mm); and 50 mmol L1 , pH ¼ 5.50 ammonium acetate buffer : acetonitrile : methanol (55 : 22 : 23 v/v) as the mobile phase with a flow rate of 0.8 mL min1 . The suggested method presented precision (intra-assay and inter-assay), linearity and limit of quantification (LOQ) all adequate for the therapeutic drug monitoring (TDM) of AEDs in plasma.

Análise quimico-farmacêutica de Darunavir etanolato em comprimidos e de seu complexo de inclusão

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

High precision and selectivity for quantitation of enrofloxacin and ciprofloxacin in five chicken tissues using solid phase extraction and ESI LC-MS/MS for application in monitoring residues

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

LC-MS/MS quantitative determination of tetrapterys mucronata alkaloids, a plant occasionally used in ayahuasca preparation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Sulfamethoxazole and ciprofloxacin removal using a horizontal-flow anaerobic immobilized biomass reactor

The antibiotics sulfamethoxazole (SMTX) and ciprofloxacin (CIP) are commonly used in human and veterinary medicine, which explains their occurrence in wastewater. Anaerobic reactors are low-cost, simple and suitable technology to wastewater treatment, but there is a lack of studies related to the removal efficiency of antibiotics. To overcome this knowledge gap, the objective of this study was to evaluate the removal kinetics of SMTX and CIP using a horizontal-flow anaerobic immobilized biomass reactor. Two different concentrations were evaluated, for SMTX 20 and 40 μg L(-1); for CIP 2.0 and 5.0 μg L(-1). The affluent and effluent analysis was carried out in liquid chromatography/tandem mass spectrometry (LC-MS/MS) with the sample preparation procedure using an off-line solid-phase extraction. This method was developed, validated and successfully applied for monitoring the affluent and effluent samples. The removal efficiency found for both antibiotics at the two concentrations studied was 97%. Chemical oxygen demand (COD) exhibited kinetic constants that were different from that observed for the antibiotics, indicating the absence of co-metabolism. Also, though the antibiotic concentration was increased, there was no inhibitory effect in the removal of COD and antibiotics.

Dinâmica de glyphosate em plantas de eucalipto

Pós-graduação em Agronomia (Proteção de Plantas) - FCA

Evaluation and degradation chemistry of orbifloxacin using LC-MS

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determination of dimethyltryptamine and beta-carbolines (ayahuasca alkaloids) in plasma samples by LC-MS/MS

Background: Ayahuasca is a psychoactive plant beverage originally used by indigenous people throughout the Amazon Basin, long before its modern use by syncretic religious groups established in Brazil, the USA and European countries. The objective of this study was to develop a method for quantification of dimethyltryptamine and beta-carbolines in human plasma samples. Results: The analytes were extracted by means of C18 cartridges and injected into LC-MS/MS, operated in positive ion mode and multiple reaction monitoring. The LOQs obtained for all analytes were below 0.5 ng/ml. By using the weighted least squares linear regression, the accuracy of the analytical method was improved at the lower end of the calibration curve (from 0.5 to 100 ng/ml; r(2)> 0.98). Conclusion: The method proved to be simple, rapid and useful to estimate administered doses for further pharmacological and toxicological investigations of ayahuasca exposure.

Metronidazole Immediate Release Formulations: A Fasting Randomized Open-Label Crossover Bioequivalence Study in Healthy Volunteers

Metronidazole is a BCS (Biopharmaceutics Classification System) class 1 drug, traditionally considered the choice drug in the infections treatment caused by protozoa and anaerobic microorganisms. This study aimed to evaluate bioequivalence between 2 different marketed 250 mg metronidazole immediate release tablets. A randomized, open-label, 2 x 2 crossover study was performed in healthy Brazilian volunteers under fasting conditions with a 7-day washout period. The formulations were administered as single oral dose and blood was sampled over 48 h. Metronidazole plasma concentrations were determined by a liquid chromatography mass spectrometry (LC-MS/MS) method. The plasma concentration vs. time profile was generated for each volunteer and the pharmacokinetic parameters C-max, T-max, AUC(0-t), AUC(0-infinity), k(e), and t(1/2) were calculated using a noncompartmental model. Bioequivalence between pharmaceutical formulations was determined by calculating 90% CIs (Confidence Intervall) for the ratios of C-max, AUC(0-t), and AUC(0-infinity) values for test and reference using log-transformed data. 22 healthy volunteers (11 men, 11 women; mean (SD) age, 28 (6.5) years [range, 21-45 years]; mean (SD) weight, 66 (9.3) kg [range, 51-81 kg]; mean (SD) height, 169 (6.5) cm [range, 156-186 cm]) were enrolled in and completed the study. The 90% CIs for C-max (0.92-1.06), AUC(0-t) (0.97-1.02), and AUC(0-infinity) (0.97-1.03) values for the test and reference products fitted in the interval of 0.80-1.25 proposed by most regulatory agencies, including the Brazilian agency ANVISA. No clinically significant adverse effects were reported. After pharmacokinetics analysis, it concluded that test 250 mg metronidazole formulation is bioequivalent to the reference product according to the Brazilian agency requirements.

Assessment of the presence of pharmaceutical compounds in seawater samples from coastal area of Gran Canaria Island (Spain)

[EN]This study presents the evaluation of seven pharmaceutical compounds belonging to different commonly used therapeutic classes in seawater samples from coastal areas of Gran Canaria Island. The target compounds include atenolol (antihypertensive), acetaminophen (analgesic), norfloxacin and ciprofloxacin (antibiotics), carbamazepine (antiepileptic) and ketoprofen and diclofenac (anti-inflammatory). Solid phase extraction (SPE) was used for the extraction and preconcentration of the samples, and liquid chromatography tandem mass spectrometry (LC-MS/MS) was used for the determination of the compounds. Under optimal conditions, the recoveries obtained were in the range of 78.3% to 98.2%, and the relative standard deviations were less than 11.8%. The detection and quantification limits of the method were in the ranges of 0.1–2.8 and 0.3–9.3 ng·L−1, respectively. The developed method was applied to evaluate the presence of these pharmaceutical compounds in seawater from four outfalls in Gran Canaria Island (Spain) during one year. Ciprofloxacin and norfloxacin were found in a large number of samples in a concentration range of 9.0–3551.7 ng·L−1. Low levels of diclofenac, acetaminophen and ketoprofen were found sporadically.