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1.
J Chromatogr A ; 1623: 461210, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32505294

RESUMO

Illegal dietary supplements adulterated with phosphodiesterase type 5 inhibitors (PDE-5i) are increasingly widely distributed through internet markets and underground routes. For this reason, it demands development of reliable screening methods to determine a wide range of PDE-5i drugs in various types of dietary supplements. Herein, we developed a screening method using gas chromatography-mass spectrometry (GC-MS) for simultaneous detection of 53 PDE-5i drugs in supplements. Common formulations (such as capsule, powder, pill, and tablet) of supplements with complicated matrices were treated by simple liquid-liquid extraction and trimethylsilyl (TMS) derivatization. With the aid of TMS derivatization, 53 PDE-5i drugs could be successfully separated and detected within 15 min, using a short microbore GC column (15 m). Moreover, owing to enhanced detection sensitivity and selectivity of PDE-5i TMS derivatives, 0.5 mg of sample was sufficient to screen and confirm targeted PDE-5i drugs. In this study, specific common ions according to structural characteristics of PDE-5i drugs were found under the electron ionization (EI) of their TMS derivatives. These specific common fragments could reflect the common pharmacophores for 4 classes of PDE-5i drugs (sildenafil, other sildenafil, vardenafil, and tadalafil analogues). Based on characteristic EI fragment ions, extracted common ion chromatograms (ECICs) and discriminant analysis (DA) were effectively used for reliable screening and classification of various types of PDE-5i drugs. Specific ECICs and DA using characteristic EI fragments here will aid in identification of newly emerging PDE-5i counterfeits in supplements. This study will be helpful to supervise illegal adulteration of PDE-5i drugs in dietary supplements to protect public health and consumer safety.


Assuntos
Suplementos Nutricionais/análise , Avaliação Pré-Clínica de Medicamentos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Inibidores da Fosfodiesterase 5/análise , Análise Discriminante , Íons , Citrato de Sildenafila/análise , Tadalafila/análise , Fatores de Tempo , Dicloridrato de Vardenafila/análise
2.
J Pharm Biomed Anal ; 177: 112872, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31525574

RESUMO

It is often reported that falsified medicines have harmful effects on patients both Japan and abroad. In this study, we purchased vardenafil tablets on the internet and investigated their quality and authenticity using visual observations, authenticity investigations, non-destructive tests (handheld NIR and Raman spectroscopy), and quality analyses (active ingredient content and tablet dissolution rate). We used genuine 20-mg Levitra tablets that were sold in Japan and tablets from Bayer AG (Germany) as controls. In April 2015, we obtained 28 samples from 15 websites on the internet. Our authenticity investigations revealed that 11 (40%) were genuine products and 17 (60%) were falsified products. Handheld NIR and Raman results revealed that the falsified products had different spectra to the genuine products. Principal component analysis of the NIR and Raman spectra showed variation among the falsified products. The 11 genuine products were of good quality, and the 17 falsified products were of poor quality. The falsified products contained sildenafil (the active ingredient of Viagra) or tadalafil (the active ingredient of Cialis) instead of vardenafil. Our results show that falsified Vardenafil tablets are sold on the internet and that it is important to prevent illegal internet sales and increase consumer awareness of the presence of falsified medicines.


Assuntos
Medicamentos Falsificados/análise , Disponibilidade de Medicamentos Via Internet/normas , Controle de Qualidade , Agentes Urológicos/análise , Dicloridrato de Vardenafila/análise , Medicamentos Falsificados/química , Medicamentos Falsificados/economia , Humanos , Japão , Disponibilidade de Medicamentos Via Internet/economia , Análise de Componente Principal , Citrato de Sildenafila/análise , Análise Espectral Raman , Comprimidos , Tadalafila/análise , Agentes Urológicos/química , Agentes Urológicos/economia , Agentes Urológicos/normas , Dicloridrato de Vardenafila/química
3.
J Pharm Biomed Anal ; 174: 198-205, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31174131

RESUMO

In this paper, we propose a novel framework to select the most relevant X-Ray Fluorescence (XRF) energy values (i.e., features) to enhance the clustering (grouping) of counterfeit and illicit medical tablets. The framework is based on the integration of multidimensional scaling (MDS) and Procrustes analysis (PA) multivariate techniques. MDS provides a projection of the original data into a lower dimension, while PA finds a projection matrix from the original data. Such outputs give rise to a feature importance index that guides an iterative feature selection process; after each feature is inserted in the subset, an optimization procedure based on a greedy search method is carried out to maximize the clustering quality assessed through the Silhouette Index (SI). The inorganic chemical fingerprinting of 41 commercial samples (Viagra®, Cialis®, Lazar®, Libiden®, Maxfil®, Plenovit®, Potent 75®, Rigix®, V-50®, Vimax® and Pramil®) and 56 seized counterfeit samples (Viagra and Cialis) was used to validate the proposed framework. From the original 2048 data points in the full spectra, we identified a subset comprised of 41 energy values that substantially improved clustering quality; the obtained groups were assessed by visual inspection of the PCA plots.


Assuntos
Medicamentos Falsificados/análise , Inibidores da Fosfodiesterase 5/análise , Espectrometria por Raios X/métodos , Análise por Conglomerados , Análise Multivariada , Análise de Componente Principal , Citrato de Sildenafila/análise , Comprimidos , Tadalafila/análise
4.
J Pharm Biomed Anal ; 173: 47-55, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31112851

RESUMO

The chirality of a dipropylaminopretadalafil stereoisomer isolated from a health supplement has been studied. Under high resolution mass spectrometry (HRMS) study, this unknown compound seems to be one of the trans configuration tadalafil analogues i.e. (6S, 12aR) or (6R, 12aS), owing to the same precursor ion at m/z 492 with mass errors within ±2 ppm tolerance and very close retention times. Moreover, the MS2 fragmentation pattern is also very similar to the two trans isomers. Fortunately, the unknown compound can be distinguished from the two trans isomers by enantioselective separation with the use of a chiral column. Further comparison studies with a series of homologous compounds without a diketopiperazine ring on ellipticity and optical rotation support the unknown compound to be in the cis-(6R, 12aR) configuration. The nuclear magnetic resonance (NMR) in one dimensional (1D) and nuclear overhauser effect spectroscopy (NOESY) have affirmed the abovementioned configuration.


Assuntos
Suplementos Nutricionais/análise , Contaminação de Medicamentos/prevenção & controle , Tadalafila/análogos & derivados , Dicroísmo Circular , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estereoisomerismo , Tadalafila/análise , Tadalafila/química
5.
J Sep Sci ; 42(8): 1509-1519, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30741483

RESUMO

A novel method for hierarchical screening of illegal adulterants in Fur seal ginseng pills products was developed by multi-dimensional fingerprint profiling analysis. Fingerprint feature of the samples was acquired by high-performance liquid chromatography analysis of 11 batches of samples with diode array detector and fluorescence detector, and then potential illegal adulterants including phosphodiesterase type-5 inhibitors, androgens, α receptor antagonists and yohimbine, were further separated at multiple wavelengths to reduce or remove interferences from sample matrix for highlight their chromatographic characteristics. Accordingly, a hierarchical screening strategy was designed by first-order and second-order fingerprints combined with spectral examination to achieve high accuracy and reliability. The method was successfully applied to screening of illegal adulterants in real samples, and it also exhibited good quantification performance through validation tests. From 16 batches of samples, three suspected samples were confirmed to be positive, containing 9.37µg/g of testosterone, 18.8 µg/g of tadalafil, and 48.5 µg/g of sildenafil, respectively. The recoveries and relative standard deviations were in the range of 83.6-103.1% and 4.2-6.8%, respectively. The proposed method provided a simple, efficient and promising alternative to monitoring functional foods.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos/legislação & jurisprudência , Panax/química , Alimento Funcional/análise , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Comprimidos/análise , Tadalafila/análise
6.
J Pharm Biomed Anal ; 166: 304-309, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30685655

RESUMO

Erectile dysfunction medicines such as Cialis and Viagra are very popular worldwide and are between the most prevalent counterfeit medicines in Brazil. A range of analytical methods has been used to analyze Cialis and Viagra, such as ATR-FTIR, GCMS and UPLC-MS. Until now, there are no data available of DSC methods for analysis of counterfeit medicines of Cialis and Viagra. DSC is a thermal analysis that provides useful information of physico-chemical events, and however is almost not used for forensic purposes. In this study, thermal analysis of 25 counterfeit Viagra and Cialis seized by Brazilian Federal Police were performed by DSC and compared to their authentic medicines and analytical standards, along with chemometric tools. Authentic samples of Viagra displayed a similar thermal profile with the API, while Cialis were different with additional endothermic peaks, that could be related to excipients interference. Thermograms of Viagra counterfeit samples were similar to authentic samples, while Cialis showed an enlargement and displacement of endothermic peaks. Also, some Cialis counterfeit samples showed melting peaks attributed to sildenafil, the API of Viagra, instead tadalafil, confirming previous results obtained by UPLC-MS. Multivariate analysis with application of Hierarchical Cluster Analysis classified different groups of samples, including a cluster with counterfeit Cialis and Viagra, indicating the use of same API for both counterfeit medicines and possibly the same illicit production; and a cluster with authentic Viagra and counterfeit Cialis, confirming the addition of sildenafil instead tadalafil to Cialis counterfeit samples. Here for the first time we described the use of DSC for chemical profiling of Cialis and Viagra and showed that even when applied to a small group of samples, DSC along with chemometric tools can be considered as a good auxiliary method in forensic casework samples. DSC provided useful data to perform the identification of counterfeit and authentic medicines, with low cost and a simple method.


Assuntos
Varredura Diferencial de Calorimetria , Medicamentos Falsificados/análise , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Tadalafila/análise , Brasil , Análise por Conglomerados , Disfunção Erétil/tratamento farmacológico , Excipientes/química , Humanos , Masculino , Inibidores da Fosfodiesterase 5/normas , Análise de Componente Principal , Citrato de Sildenafila/normas , Tadalafila/normas
7.
J Pharm Biomed Anal ; 158: 494-503, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29966946

RESUMO

The commerce of falsified drugs has substantially grown in recent years due to facilitated access to technologies needed for copying authentic pharmaceutical products. Attenuated Total Reflectance coupled with Fourier Transform Infrared (ATR-FTIR) spectroscopy has been successfully employed as an analytical tool to identify falsified products and support legal agents in interrupting illegal operations. ATR-FTIR spectroscopy typically yields datasets comprised of hundreds of highly correlated wavenumbers, which may compromise the performance of classical multivariate techniques used for sample classification. In this paper we propose a new wavenumber interval selection method aimed at selecting regions of spectra that best discriminate samples of seized drugs into two classes, authentic or falsified. The discriminative power of spectra regions is represented by an Interval Importance Index (III) based on the Two-Sample Kolmogorov-Smirnov test statistic, which is a novel proposition of this paper. The III guides an iterative forward approach for wavenumber selection; different data mining techniques are used for sample classification. In 100 replications using the best combination of classification technique and wavenumber intervals, we obtained average 99.87% accurate classifications on a Cialis® dataset, while retaining 12.5% of the authentic wavenumbers, and average 99.43% accurate classifications on a Viagra® dataset, while retaining 23.75% of the authentic wavenumbers. Our proposition was compared with alternative approaches for individual and interval wavenumber selection available in the literature, always leading to more consistent and easier to interpret results.


Assuntos
Medicamentos Falsificados/análise , Fraude/prevenção & controle , Modelos Químicos , Inibidores da Fosfodiesterase 5/análise , Agentes Urológicos/análise , Brasil , Medicamentos Falsificados/uso terapêutico , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/análise , Citrato de Sildenafila/uso terapêutico , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Estatísticas não Paramétricas , Tadalafila/análise , Tadalafila/uso terapêutico , Agentes Urológicos/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-29601254

RESUMO

A novel compound structurally similar to tadalafil was found in a dietary supplement by adulterants screening test and isolated by column chromatography. After analysis by accurate mass, nuclear magnetic resonance (NMR) and X-ray, the structure of this novel tadalafil analogue was determined as (5R, 16R)-5-(1,3-benzodioxol-5-yl)-2- (3-ethypentan-3-yl)-15,16-dihydro(1H-imidazo[1,5-a]pyrido)[3,4-b]indol-1,3-dion.


Assuntos
Suplementos Nutricionais/análise , Tadalafila/análise , Cromatografia Líquida , Cromatografia em Camada Delgada , Cristalografia por Raios X , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Tadalafila/análogos & derivados , Espectrometria de Massas em Tandem
9.
J Colloid Interface Sci ; 512: 379-388, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29080533

RESUMO

Graphene (GR) is one of the most promising candidates for utilization in the electroanalytical field because of its superior electrocatalytic activity, excellent electronic conductivity, and high chemical stability. However, the GR sheets usually tend to stack together with π-π interaction. The spontaneous stacking leads to the aggregation of the GR sheets and imposes a negative feedback in the surface area of the GR, which obviously limits its electrochemical application. In this study, nitrogen-doped porous GR (NPGR) with different pore sizes is prepared by using silica (SiO2) as a template. The NPGR exhibits high surface area and porous structure, fulfilling the requirement for supporting materials. Being a support, the structural uniqueness and N dopants of NPGR facilitate the deposition of Pt nanoparticles (Pt NPs). The Pt NPs/NPGR composites integrate the structural properties of NPGR and catalytic properties of Pt NPs. A selective and sensitive electrochemical sensor was successfully developed for sensitive determination of Tadalafil (TAD), showing a concentration range of 1.30-488.9µM and limit of detection of 0.268µM.


Assuntos
Técnicas Biossensoriais , Grafite/química , Nanopartículas Metálicas/química , Nitrogênio/química , Platina/química , Dióxido de Silício/química , Tadalafila/análise , Catálise , Técnicas Eletroquímicas , Limite de Detecção , Porosidade
10.
Biomed Chromatogr ; 31(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28558416

RESUMO

Tadalafil is used for the treatment of erectile dysfunction. Its related patents expired in 2016, and so related generic drug production is predicted to be increased. This work is focused on developing a fast ultra-high-performance liquid chromatography with diode array detection and/or mass spectrometry detection for the separation and determination of tadalafil and its impurities in pharmaceutical samples. A modern reversed-phase stationary phase with sub-2 µm particle size, Zorbax StableBond Rapid Resolution High Definition with octylsilane chemically bonded phase to totally porous silica particles, was used for the solving this problem. Column temperature was set at 40 ± 0.1°C. A mobile phase consisting of acetonitrile and aqueous solution of 0.1% (v/v) trifluoroacetic acid for diode array detection detection and 0.05% (v/v) formic acid, both running at a flow rate of 0.62 mL/min, were used to achieve the required separation of all components within a 5 min run. The limit of detection was 3.5 µg/L and the limit of quantification was 10.0 µg/L for the method for both UV and MS detectors. Accurate mass spectra of tadalafil's related impurities are shown for advanced confirmation. The method is directly transferable to routine analysis of tadalafil in pharmaceutical and control laboratories.


Assuntos
Espectrometria de Massas/métodos , Tadalafila/análise , Tadalafila/química , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
11.
Chem Pharm Bull (Tokyo) ; 65(5): 498-503, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28458371

RESUMO

A number of phosphodiesterase 5 (PDE5) inhibitors approved by authorities have been used successfully in the treatment of erectile dysfunction. These medicines must be prescribed carefully due to their adverse effects, but they and their analogues are being illegally added to dietary supplements. These illegal dietary supplements pose a significant risk to public health. Several dimeric tadalafil analogues have been synthesized for use as reference standards in the inspection of functional foods that are mainly advertised as sexual enhancement products. During the course of this synthesis, 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate (HATU) was proven to be the reagent of choice for amide coupling to produce these dimeric tadalafil analogues. Moreover, the trans-isomer structures tentatively assigned for the isolated dimeric tadalafil analogues (bisprehomotadalafil and bisprecyclopentyltadalafil) found in dietary supplements are now revised to cis-isomer structures.


Assuntos
Suplementos Nutricionais/análise , Tadalafila/análise , Tadalafila/síntese química , Humanos , Estrutura Molecular , Estereoisomerismo , Tadalafila/administração & dosagem
12.
J Mass Spectrom ; 52(7): 411-416, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28470986

RESUMO

A facile method based on electrospray mass spectrometry was established and validated for the differentiation of enantiomeric tadalafil isomers without using chiral chromatographic separation. The enantiomers were coupled with a chiral selector to form diastereomeric complex ions. Nickel-tadalafil complexes, [NiII (tadalafil)(l-Trp)-H]+ , produced a characteristic fragment ion at m/z 524 by loss of 1-methyl-1,6-dihydropyrazine-2,5-dione via collision-induced dissociation. The relative abundance of this fragment ion to the precursor contributed to differentiate tadalafil enantiomers, and energy-resolved product-ion spectra were applied to determine the molar composition of tadalafil in the mixture (R,R and S,S) as well. In addition, the other two forms of stereomeric isomers of tadalafil (R,S and S,R) could be also distinguished and analyzed by this method. The method was validated in different types of mass spectrometers (AB quadrupole time-of-flight and Bruker ion trap) and also verified by a chiral high-performance liquid chromatography coupled with quadrupole time-of-flight. The chiral determination of tadalafil using MS method proved to be rapid (1-min run time for each sample) and to have the same accuracy and precision comparable to chiral liquid chromatography mass spectrometry methods. This method provides an alternative to commonly used chromatographic technique for chiral determination and is particularly useful in rapid screening in enantioselective synthesis and enantiomeric impurity detection in pharmaceutical industry. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Complexos de Coordenação/análise , Níquel/química , Inibidores da Fosfodiesterase 5/análise , Tadalafila/análise , Cromatografia Líquida de Alta Pressão/métodos , Complexos de Coordenação/química , Contaminação de Medicamentos , Conformação Molecular , Inibidores da Fosfodiesterase 5/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Estereoisomerismo , Tadalafila/química
13.
Biosens Bioelectron ; 89(Pt 1): 361-369, 2017 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-27436432

RESUMO

The present work described the comparison of ß-cyclodextrin (ß-CD) and p-sulfonated calix[6]arene (SCX6) functionalized reduced graphene oxide (RGO) for recognition of tadalafil. In this study, tadalafil and two macrocycles (ß-CD and SCX6) were selected as the guest and host molecules, respectively. The inclusion complexes of ß-CD/tadalafil and SCX6/tadalafil were studied by UV spectroscopy and molecular simulation calculations, proving the higher supermolecular recognition capability of SCX6 than ß-CD towards tadalafil. The ß-CD@RGO and SCX6@RGO composites were prepared by a wet-chemical route. The obtained composites were characterized by Fourier transform infrared spectrometry, thermogravimetric analysis, atomic force microscopy, and zeta potential. The SCX6@RGO showed a higher electrochemical response than ß-CD@RGO, which was caused by the higher recognition capability of SCX6 than ß-CD. By combining the merits of SCX6 and the RGO, a sensitive electrochemical sensing platform was developed based on the SCX6@RGO nanohybrids. A linear response range of 0.1-50 µM and 50-1000 µM for tadalafil with a low detection limit of 0.045 µM (S/N=3) was obtained by using this method. The constructed sensing platform was successfully used to determine tadalafil in herbal sexual health products and spiked human serum samples, suggesting its promising analytical applications for the trace level determination of tadalafil.


Assuntos
Calixarenos/química , Técnicas Eletroquímicas/métodos , Grafite/química , Fenóis/química , Tadalafila/sangue , Vasodilatadores/sangue , beta-Ciclodextrinas/química , Técnicas Biossensoriais/métodos , Humanos , Limite de Detecção , Modelos Moleculares , Simulação de Acoplamento Molecular , Oxirredução , Óxidos/química , Plantas Medicinais/química , Sulfonas/química , Tadalafila/análise , Vasodilatadores/análise
14.
Artigo em Inglês | MEDLINE | ID: mdl-28004593

RESUMO

A new tadalafil analogue was found in a commercial dietary supplement for enhancing sexual performance. The compound was detected by a high-performance liquid chromatography-diode array detector (HPLC-DAD). The analogue was isolated using semi-preparative HPLC, and its accurate mass was established by two LC-high-resolution-mass spectrometers (LC-HRMS). The structure was determined by nuclear magnetic resonance (NMR) spectroscopy. The accurate mass of the compound corresponded to a molecular formula of C24H23N3O4. The compound was identified as a structural analogue of tadalafil in which the N-methyl group of tadalafil was replaced with an N-isopropyl group. We have named the new analogue isopropylnortadalafil and it is first reported herein.


Assuntos
Suplementos Nutricionais/análise , Tadalafila/análogos & derivados , Tadalafila/análise , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Conformação Molecular , Tadalafila/química
15.
J Chromatogr Sci ; 55(3): 232-242, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-27881492

RESUMO

High-performance liquid chromatography coupled to tandem mass spectrometry was used to develop and validate a rapid method to qualitatively and quantitatively analyse 18 common adulterants in herbal medicine and food samples. Initially, the mobile phase composition was optimized in three different columns: core-shell, monolithic and standard 3.5-µm-particle-size columns. The results show that the core-shell column provides the best separation. Moreover, the tandem mass spectrometry was optimized. The linear range for all adulterants was 0.5-500 µg mL-1. Finally, the samples that were supplied by the Public Authority of Customer Protection, Ministry of Health, and those collected from the local market were analysed. The results indicate that 7 of 33 analysed samples contained adulterants. The adulterated samples mainly contain sildenafil, tadalafil or vardenafil. The concentrations of these three adulterants in the samples were 0.18-39 wt%. This study is the first report in the Sultanate of Oman about adulteration in herbal medicine and food samples. The results clearly raise some concern and require proper plan of action to increase public awareness about this serious issue.


Assuntos
Cromatografia Líquida/métodos , Contaminação de Medicamentos , Análise de Alimentos/métodos , Contaminação de Alimentos , Preparações de Plantas/análise , Espectrometria de Massas em Tandem/métodos , Produtos Domésticos/análise , Produtos Domésticos/normas , Omã , Preparações de Plantas/química , Citrato de Sildenafila/análise , Tadalafila/análise , Dicloridrato de Vardenafila/análise
16.
J Pharm Biomed Anal ; 128: 360-366, 2016 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-27337189

RESUMO

A screen for known PDE-5 inhibitors in a dietary supplement product marketed for "enhanced sexual performance" detected a compound that structurally resembled chloropretadalafil, a known analog of tadalafil. The compound was isolated from the supplement matrix using high performance liquid chromatography with ultraviolet detection (HPLC-UV) and a fraction collector, and was further characterized using gas chromatography with Fourier Transform infrared detection and mass spectral detection (GC/FT-IR/MS), as well as high resolution mass spectrometry (HRMS). The analog had an accurate mass of m/z 441.1216 (error is 0.8706ppm) for the protonated species [M+H](+), corresponding to a molecular formula of C23H22ClN2O5. HRAM and GC/FT-IR/MS mass spectral fragmentation data suggested that the modification is a chloropropanoyl moiety extending from the nitrogen on the piperidine ring of chloropretadalafil. The proposed new analog has been named chloropropanoylpretadalafil.


Assuntos
Suplementos Nutricionais/análise , Tadalafila/análogos & derivados , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Tadalafila/análise , Tadalafila/isolamento & purificação
17.
J AOAC Int ; 99(4): 923-928, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27143116

RESUMO

A sensitive analytical method was developed for the simultaneous determination of sildenafil and tadalafil in legal drugs, illicit/counterfeit drugs, and wastewater samples. Chromatographic separation of two analytes was achieved on a C18 column with a mobile phase including 50 mM phosphate buffer at pH 6.0 and acetonitrile (35 + 65, v/v) at the flow rate of 1.0 mL/min. Analytes were separated from each other in 6 min with high resolution. LOD/LOQ values were calculated as 28/92 ng/mL for sildenafil citrate and 39/129 ng/mL for tadalafil. Calibration plots for both analytes were linear with correlation coefficients >0.9993. A validated method was successfully applied to legal and illicit erectile-dysfunction drug samples consumed in Istanbul, Turkey, and to wastewater samples. Nine different samples were analyzed for qualitative and quantitative measurement of their ingredients, and the results were compared with the values written on the labels of the drugs. The wastewater sample was also analyzed for its sildenafil and tadalafil content. To calculate the recoveries, a spiking experiment was performed and recovery rates for sildenafil and tadalafil were calculated as 101.30 ± 3.43 and 102.68 ± 1.59, respectively.


Assuntos
Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Tadalafila/análise , Vasodilatadores/análise , Cromatografia Líquida de Alta Pressão , Medicamentos Falsificados/análise , Drogas Ilícitas/análise , Águas Residuárias/química
18.
Artigo em Inglês | MEDLINE | ID: mdl-27143524

RESUMO

A novel tadalafil analogue in a dietary supplement was found by drug-adulteration screening and isolated by column chromatography and HPLC. Based on extensive 1D- and 2D-NMR and mass spectral analyses, the structure of this new compound was determined as 2-(N,N-dipropyl acetyl) 3-methyl 1-(benzo[d][1,3]dioxol-5-yl)-3,4-dihydro-1H-pyrido[3,4-b]indole-3-carboxylate - its common name is dipropylaminopretadalafil.


Assuntos
Tadalafila/análogos & derivados , Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais/análise , Contaminação de Medicamentos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Tadalafila/análise , Tadalafila/química
19.
Pharm Dev Technol ; 21(5): 583-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25996632

RESUMO

Although the fragmentation of the active pharmaceutical ingredient (API) is a phenomenon that is mentioned in many literature sources, no well-suited analytical tools for its investigation are currently known. We used the hot-stage microscopy method, already presented in our previous work, and studied the real fragmentation of the tadalafil particles in model tablets which were prepared under different compaction pressures. The morphology, spectral imaging and evaluation of plastic and elastic energies were also analyzed to support the hot-stage method. The prepared blend of tadalafil and excipients was compacted under a several forces from 5 to 35 kN to reveal the trend of fragmentation. The exact fragmentation of tadalafil with increased compaction pressure was revealed by the hot-stage microscopic method and it was in good agreement with plastic and elastic energies. Conversely, spectral imaging, which is being used for this analysis, was considered to be inaccurate methodology as mainly agglomerates, not individual particles, were measured. The availability of the hot-stage microscopic method equips pharmaceutical scientists with an in vitro assessment technique that will more reliably determine the fragmentation of the API in finished tablets and the behavior of the particles when compacted.


Assuntos
Temperatura Alta , Microscopia Eletrônica de Varredura/métodos , Tadalafila/química , Tecnologia Farmacêutica/métodos , Tamanho da Partícula , Comprimidos , Tadalafila/análise
20.
Luminescence ; 31(1): 173-8, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26019060

RESUMO

A valid, sensitive and rapid spectrofluorimetric method has been developed and validated for determination of both tadalafil (TAD) and vardenafil (VAR) either in their pure form, in their tablet dosage forms or spiked in human plasma. This method is based on measurement of the native fluorescence of both drugs in acetonitrile at λem 330 and 470 nm after excitation at 280 and 275 nm for tadalafil and vardenafil, respectively. Linear relationships were obtained over the concentration range 4-40 and 10-250 ng/mL with a minimum detection of 1 and 3 ng/mL for tadalafil and vardenafil, respectively. Various experimental parameters affecting the fluorescence intensity were carefully studied and optimized. The developed method was applied successfully for the determination of tadalafil and vardenafil in bulk drugs and tablet dosage forms. Moreover, the high sensitivity of the proposed method permitted their determination in spiked human plasma. The developed method was validated in terms of specificity, linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), precision and accuracy. The mean recoveries of the analytes in pharmaceutical preparations were in agreement with those obtained from the comparison methods, as revealed by statistical analysis of the obtained results using Student's t-test and the variance ratio F-test.


Assuntos
Preparações Farmacêuticas/química , Inibidores de Fosfodiesterase/análise , Inibidores de Fosfodiesterase/sangue , Tadalafila/análise , Tadalafila/sangue , Dicloridrato de Vardenafila/análise , Dicloridrato de Vardenafila/sangue , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Espectrometria de Fluorescência , Tensoativos/química
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