Publications by authors named "Leandro Augusto Calixto"

10 Publications

  • Page 1 of 1

Developing an analytical method by HPLC for simultaneous quantification of methylene blue and metformin applied to in vitro skin permeation and retention studies.

Biomed Chromatogr 2021 Mar 5:e5112. Epub 2021 Mar 5.

Institute of Environmental, Chemical and Pharmaceutical Sciences, Department of Pharmaceutical Sciences, Federal University of São Paulo (Unifesp), Diadema, São Paulo, Brazil.

The aim of this study was to develop an HPLC method for simultaneous quantification of metformin (MET) and methylene blue (MB) in in vitro skin permeation/retention studies, in which retention was evaluated in the different layers of the skin [stratum corneum (SC) and the viable epidermis + dermis (VE + D)]. The method was validated considering the following parameters: specificity, linearity, quantitation limit (LOQ), recovery, precision and accuracy. Calibration curves were obtained using the following six matrices: methanol, water, methanolic extracts from the SC and VE + D spiked with the drugs and drugs extracted from the SC and VE + D. The precision, accuracy and LOQ of the method were evaluated in water and in VE + D and SC, applying the drug extraction process. The results show that the method is selective and linear for both drugs. The precision and accuracy values, independent of matrix and drug, were below the limit of 15%. The LOQ of MB was defined as 0.4 μg/ml in the VE + D and SC and 0.8 μg/ml in water. The LOQ of MET was defined as 0.8 μg/ml in the VE + D and SC and 0.4 μg/ml in the water. The recovery of the method was adequate, consistent and reproducible for the concentration range of 0.4-10 μg/ml for MB (73.3-92.1%) and 0.8-10.0 μg/mL for MET (72.4-94.4%). This method has a potential application in the development of formulation for skin delivery of MB and MET.
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http://dx.doi.org/10.1002/bmc.5112DOI Listing
March 2021

Pharmaceutical market, environmental public policies and water quality: the case of the São Paulo Metropolitan Region, Brazil.

Cad Saude Publica 2020 23;36(11):e00192319. Epub 2020 Nov 23.

Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo, Diadema, Brasil.

Water pollution has been an increasing concern for the authorities responsible for planning and executing public policies. In this qualitative research, we have discussed the most sold pharmaceuticals in the São Paulo Metropolitan Region, Brazil, and compared public policies focused on pharmaceuticals and environmental issues among countries/regions. For that, data provided by Close-Up International related to the sales of medicines in the São Paulo Metropolitan Region between April/2016 and April/2017 were collected and processed to identify and quantify the pharmaceutical products. The 300 most sold medicines in the São Paulo Metropolitan Region fall in 26 therapeutic classes, which include 159 drugs. The most sold pharmaceutical products group is nonsteroidal anti-inflammatory drugs (NSAIDs) representing approximately 44.3% of the total. The ten most sold pharmaceuticals sum up 1200 tons. Dipyrone is the first place in mass representing around 488 tons, followed by metformin with around 310 tons commercialized. Public policies focused on pharmaceuticals in the environment still need adjustments to improve reinforcement, even in developed countries. There is no international standard on how to conduct the issue, each country adopting the public policy that best matches to the local. Brazil, despite having some legislation that approaches the theme, still lacks effective public policies and stakeholder awareness. In this aspect, the need for improvement of the reverse logistics system, consumer orientation to the adequate disposal of unused/expired medicines, and the adoption of the unit-dose system as a therapeutic strategy is evident.
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http://dx.doi.org/10.1590/0102-311X00192319DOI Listing
March 2021

A new medium-throughput screening design approach for the development of hydroxymethylnitrofurazone (NFOH) nanostructured lipid carrier for treating leishmaniasis.

Colloids Surf B Biointerfaces 2020 Sep 1;193:111097. Epub 2020 May 1.

University of São Paulo, Faculty of Pharmaceutical Sciences, São Paulo, SP, Brazil. Electronic address:

Hydroxymethilnitrofurazone (NFOH) is a nitrofurazone derivative and has potential use in treating leishmaniasis. However, due to low water solubility and bioavailability, NFOH has failed in in vivo tests. Nanostructured lipid carrier (NLC) is an alternative to overcome these limitations by improving pharmacokinetics and modifying drug delivery. This work is focused on developing a novel NFOH-loaded NLC (NLC-NFOH) using a D-optimal mixture statistical design and high-pressure homogenization, for oral administration to treat leishmaniasis. The optimized NLC-NFOH consisted of Mygliol® 840, Gelucire® 50/13, and Precirol® ATO 5 as lipids. These lipids were selected using a rapid methodology Technobis Crystal 16 T M, microscopy, and DSC. Different tools for selecting lipids provided relevant scientific knowledge for the development of the NLC. NLC-NFOH presented a z-average of 198.6 ± 5.4 nm, PDI of 0.11 ± 0.01, and zeta potential of -13.7 ± 0.7 mV. A preliminary in vivo assay was performed by oral administration of NLC-NFOH (2.8 mg/kg) in one healthy male Wistar rat (341 g) by gavage. Blood from the carotid vein was collected, and the sample was analyzed by HPLC. The plasma concentration of NFOH after 5 h of oral administration was 0.22 μg/mL. This same concentration was previously found using free NFOH in the DMSO solution (200 mg/kg), which is an almost 100-fold higher dose. This study allowed a design space development approach of the first NLC-NFOH with the potential to treat leishmaniasis orally.
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http://dx.doi.org/10.1016/j.colsurfb.2020.111097DOI Listing
September 2020

Evaluation of oral mechanical and gustatory sensitivities and salivary cotinine levels in adult smokers.

Acta Odontol Scand 2020 May 27;78(4):256-264. Epub 2019 Nov 27.

Department Pharmaceutical Sciences, Universidade Federal de São Paulo (UNIFESP), Diadema, Brazil.

The aim was to examine oral mechanical and gustatory sensitivities in adult smokers and to estimate salivary levels of cotinine by tobacco consumption. A total of 54 adults (20-45 years old; 28 males/26 females) were divided into two sex-paired groups: smoker group ( = 27), tobacco consumers with no other chronic disease/use of chronic medication, and a control non-smoker non-exposed group with similar age ( = 27). 24 h-Recall was used to gather information about tobacco consumption, date of onset and duration of the habit. Oral mechanical evaluation comprised touch detection threshold (MDT) of upper and lower lips and tongue tip and two-point discrimination (TPD) assessments. Taste sensitivities for sweet, salty, sour and bitter were evaluated in four concentrations. Salivary cotinine was determined by high performance liquid chromatography. Statistical analysis comprised Mann-Whitney, Two-way ANOVA test and regression analysis. The mean smoking time was 13.6 years (mean 8.4 mg/day; 13 cigarettes/day). A sex-effect was observed on MDT of tongue tip (higher sensitivity in females), while group-effect was observed on TPD of lower lip, showing a smaller sensitivity among smokers ( < .05; moderate effect: Eta partial = 0.076). Although the total score of gustatory sensitivity did not differ between groups, smokers exhibited an irregular pattern of correctly identified tastants among the different concentrations of salty, sour and bitter. The predictive model showed that salivary cotinine was dependent on "nicotine consumption on the day before" ( = 49%). A difference in tactile sensitivity of the lower lip and qualitative changes in taste sensitivity were observed in smokers.
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http://dx.doi.org/10.1080/00016357.2019.1694978DOI Listing
May 2020

Arsenic volatilization by Aspergillus sp. and Penicillium sp. isolated from rice rhizosphere as a promising eco-safe tool for arsenic mitigation.

J Environ Manage 2019 May 20;237:170-179. Epub 2019 Feb 20.

Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Avenida dos Estados 5001, 09210-580, Santo André, SP, Brazil. Electronic address:

Arsenic (As) is a non-threshold human carcinogenic. This element can be volatilized either by nature or anthropogenic sources. In the present study, the analytical performance of an As volatile species trapping system was evaluated to assess the As volatilization promoted by Penicillium sp. and Aspergillus sp., both isolated from rice rhizosphere, and Aspergillus niger sp. considered as a reference. The study was conducted for 60 days (sampling of volatile As species from 1st to 30 day and from 31st to 60 day). The efficiency of As-volatilization was associated with the fungal growth. The highest As volatilization occurred from 31st to 60 day. Penicillium sp., Aspergillus sp. and A. niger were capable of producing 57.8, 46.4, and 5.2% of volatile arsenic species, respectively. The speciation analysis has shown trimethylarsine (TMAs) as the main volatilized As-form, followed by mono- and dimethylarsine (MMAs and DMAs). The results are following the "Challenger pathway". Therefore, the tested fungi isolated from rice rhizosphere have shown promising properties concerning bio-volatilization with potential use for As-mitigation in paddy soils.
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http://dx.doi.org/10.1016/j.jenvman.2019.02.060DOI Listing
May 2019

Determination of Levetiracetam in Human Plasma by Dispersive Liquid-Liquid Microextraction Followed by Gas Chromatography-Mass Spectrometry.

J Anal Methods Chem 2016 17;2016:5976324. Epub 2016 Oct 17.

Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.

Levetiracetam (LEV) is an antiepileptic drug that is clinically effective in generalized and partial epilepsy syndromes. The use of this drug has been increasing in clinical practice and intra- or -interindividual variability has been exhibited for special population. For this reason, bioanalytical methods are required for drug monitoring in biological matrices. So this work presents a dispersive liquid-liquid microextraction method followed by gas chromatography-mass spectrometry (DLLME-GC-MS) for LEV quantification in human plasma. However, due to the matrix complexity a previous purification step is required. Unlike other pretreatment techniques presented in the literature, for the first time, a procedure employing ultrafiltration tubes Amicon® (10 kDa porous size) without organic solvent consumption was developed. GC-MS analyses were carried out using a linear temperature program, capillary fused silica column, and helium as the carrier gas. DLLME optimized parameters were type and volume of extraction and dispersing solvents, salt addition, and vortex agitation time. Under chosen parameters (extraction solvent: chloroform, 130 L; dispersing solvent: isopropyl alcohol, 400 L; no salt addition and no vortex agitation time), the method was completely validated and all parameters were in agreement with the literature recommendations. LEV was quantified in patient's plasma sample using less than 550 L of organic solvent.
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http://dx.doi.org/10.1155/2016/5976324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5086507PMC
October 2016

Combination of hollow-fiber liquid-phase microextraction and capillary electrophoresis for pioglitazone and its main metabolites determination in rat liver microsomal fraction.

Electrophoresis 2013 Mar 25;34(6):862-9. Epub 2013 Feb 25.

Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.

Pioglitazone (PGZ), a thiazolidinedione antidiabetic agent, is reported as a potent and selective activator of peroxisome proliferator-activated receptor γ (PPAR γ). This drug has been widely prescribed for the treatment of Type 2 diabetes mellitus. In this regard, this manuscript presents, for the first time, an alternative electrophoretic method for PGZ and its main metabolites determination in rat liver microsomal fraction. The electrophoretic analyses were performed using an uncoated fused-silica capillary of 50 μm id, 48 cm in total length and 40 cm in effective length, and 50 mmol/L sodium phosphate buffer solution (pH 2.5). All experiments were carried out under the normal mode. The capillary temperature was set at 35°C and a constant voltage of +30 kV was applied during the analyses. Samples were introduced into the capillary by hydrodynamic injection (50 mbar, 15 s) and detection was performed at 190 nm. The sample preparation procedure, based on hollow-fiber liquid-phase microextraction, was optimized using multifactorial experiments. Next, the following optimal condition was established: sample agitation at 1500 rpm, extraction for 15 min, 0.01 mol/L hydrochloric acid as acceptor phase, 1-octanol as organic phase, and donor phase pH adjustment to 6.0. The method demonstrated LOQs of 200 ng/mL. Additionally, it was linear over the concentration range of 200-25,000 ng/mL for PGZ and 200-2000 ng/mL for the metabolites. Finally, the validated method was employed to study the in vitro metabolism of PGZ using rat liver microsomal fraction.
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http://dx.doi.org/10.1002/elps.201200430DOI Listing
March 2013

Solid phase microextraction and LC-MS/MS for the determination of paliperidone after stereoselective fungal biotransformation of risperidone.

Anal Chim Acta 2012 Sep 9;742:80-9. Epub 2012 Jun 9.

Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.

The present work describes for the first time the use of SPME coupled to LC-MS/MS employing the polar organic mode in a stereoselective fungal biotransformation study to investigate the fungi ability to biotransform the drug risperidone into its chiral and active metabolite 9-hydroxyrisperidone (9-RispOH). The chromatographic separation was performed on a Chiralcel OJ-H column using methanol:ethanol (50:50, v/v) plus 0.2% triethylamine as the mobile phase at a flow rate of 0.8 mL min(-1). The SPME process was performed using a C18 fiber, 30 min of extraction time and 5 min of desorption time in the mobile phase. The method was completely validated and all parameters were in agreement with the literature recommendations. The Cunninghamella echinulata fungus was able to biotransform risperidone into the active metabolite, (+)-9-RispOH, resulting in 100% of enantiomeric excess. The Cunninghamella elegans fungus was also able to stereoselectively biotransform risperidone into (+)- and (-)-9-RispOH enantiomers at different rates.
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http://dx.doi.org/10.1016/j.aca.2012.05.056DOI Listing
September 2012

In vitro characterization of rosiglitazone metabolites and determination of the kinetic parameters employing rat liver microsomal fraction.

Eur J Drug Metab Pharmacokinet 2011 Sep 17;36(3):159-66. Epub 2011 Apr 17.

Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, 14040-903, Brazil.

Rosiglitazone (RSG), a thiazolidinedione antidiabetic drug, is metabolized by CYP450 enzymes into two main metabolites: N-desmethyl rosiglitazone (N-Dm-R) and ρ-hydroxy rosiglitazone (ρ-OH-R). In humans, CYP2C8 appears to have a major role in RSG metabolism. On the other hand, the in vitro metabolism of RSG in animals has not been described in literature yet. Based on these concerns, the kinetic metabolism study of RSG using rat liver microsomal fraction is described for the first time. Maximum velocity (V (max)) values of 87.29 and 51.09 nmol/min/mg protein were observed for N-Dm-R and ρ-OH-R, respectively. Michaelis-Menten constant (K(m)) values were of 58.12 and 78.52 μM for N-Dm-R and ρ-OH-R, respectively. Therefore, these results demonstrated that this in vitro metabolism model presents the capacity of forming higher levels of N-Dm-R than of ρ-OH-R, which also happens in humans. Three other metabolites were identified employing mass spectrometry detection under positive electrospray ionization: ortho-hydroxy-rosiglitazone (ο-OH-R) and two isomers of N-desmethyl hydroxy-rosiglitazone. These metabolites have also been observed in humans. The results observed in this study indicate that rats could be a satisfactory model for RSG metabolism.
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http://dx.doi.org/10.1007/s13318-011-0039-8DOI Listing
September 2011

Simultaneous determination of rosiglitazone and its metabolites in rat liver microsomal fraction using hollow-fiber liquid-phase microextraction for sample preparation.

J Sep Sci 2010 Sep;33(17-18):2872-80

Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

A three-phase hollow-fiber liquid-phase microextraction method for the analysis of rosiglitazone and its metabolites N-desmethyl rosiglitazone and ρ-hydroxy rosiglitazone in microsomal preparations is described for the first time. The drug and metabolites HPLC determination was carried out using an X-Terra RP-18 column, at 22°C. The mobile phase was composed of water, acetonitrile and acetic acid (85:15:0.5, v/v/v) and the detection was performed at 245 nm. The hollow-fiber liquid-phase microextraction procedure was optimized using multifactorial experiments and the following optimal condition was established: sample agitation at 1750 rpm, extraction for 30 min, hydrochloric acid 0.01 mol/L as acceptor phase, 1-octanol as organic phase, and donor phase pH adjustment to 8.0. The recovery rates, obtained by using 1 mL of microsomal preparation, were 47-70%. The method presented LOQs of 50 ng/mL and it was linear over the concentration range of 50-6000 ng/mL, with correlation coefficients (r) higher than 0.9960, for all analytes. The validated method was employed to study the in vitro biotransformation of rosiglitazone using rat liver microsomal fraction.
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http://dx.doi.org/10.1002/jssc.201000380DOI Listing
September 2010