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1.
Shokuhin Eiseigaku Zasshi ; 61(1): 34-40, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32336717

RESUMO

Some illegal dietary supplements contain phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, for exerting "therapeutic" effects in erectile dysfunction. This is apparently dangerous, and thus, should be appropriately regulated. Identification of descarbonsildenafil was first reported in Singapore in a coffee sample labeled to exert male sexual performance enhancement effects. However, it is unclear whether the compound possesses PDE5 inhibitory activity. We encountered during our survey of dietary supplements, a sexual enhancement product commercially available in Tokyo, in which a peak presumed to be of descarbonsildenafil was detected by LC-UV and electrospray ionization-tandem MS (ESI-MS/MS). The compound was isolated and identified as descarbonsildenafil with liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS), NMR, and X-ray crystal structural analysis. In addition, descarbonsildenafil showed PDE5 inhibitory activity in PDE5 inhibition assay, and its IC50 value for PDE5A1 was found to be 30 nmol/L. The results of INADEQUATE NMR and X-ray crystal structural analysis in this study provide information for the identification of descarbonsildenafil. Since this study indicates that this compound is a PDE5 inhibitor having adequate activity, it is regulated as a drug component in Japan.


Assuntos
Suplementos Nutricionais , Contaminação de Alimentos , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Espectrometria de Massas em Tandem , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Tóquio
2.
Shokuhin Eiseigaku Zasshi ; 60(4): 96-107, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31474657

RESUMO

LC/Tribrid Orbitrap was developed to determine phosphodiesterase-5 (PDE-5) inhibitors and their analogs as adulterants in dietary supplements. High-resolution MS/MS and MS3 spectra of PDE-5 inhibitors and their analogs were obtained by LC/Tribrid Orbitrap using both higher-energy collisional dissociation and collision-induced dissociation. We investigated dietary supplements that claim to enhance men's sexual performance, and detected PDE-5 inhibitors and their analogs. We also estimated the structures of the PDE-5 inhibitor analogs and the impurities of PDE-5 inhibitors and their analogs in the dietary supplements.


Assuntos
Suplementos Nutricionais/análise , Inibidores da Fosfodiesterase 5/análise , Espectrometria de Massas em Tandem , Cromatografia Líquida , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5
3.
Talanta ; 204: 36-43, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357306

RESUMO

As a widely consumed beverage, coffee tends to be a target for intentional adulteration. This study describes the application of modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) coupled to liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for simultaneous screening, identification, and quantification of undeclared phosphodiesterase 5 (PDE5) inhibitors in instant coffee premixes (ICPs). The mass spectrometer was operated in auto MS/MS acquisition for simultaneous MS and MS/MS experiments. Qualitative establishments from the suspected-target screening and targeted identification processes led to an unambiguous analyte assignment from the protonated molecule ([M+H]+) precursor ion which is subsequently used for quantification of 23 targeted PDE5 inhibitors. The analytical method validation covered specificity, linearity, range, accuracy, limit of detection (LOD), limit of quantification (LOQ), precisions, matrix effect (ME), and extraction recovery (RE). The specificity was established using the optimised chromatographic separation as well as the distinguishable [M+H]+ precursor ion. The linearity of each target analyte was demonstrated with a coefficient of determination (r2) of >0.9960 over the expected range of sample concentrations. The accuracy ranged from 88.1%-119.3% with LOD and LOQ of <70 ng/mL and 80 ng/mL, respectively. Excellent precisions were established within 0.4%-9.1% of the relative standard deviation. An insignificant ME within -5.2% to +8.7% was achieved using three different strategies of chromatography, sample extraction, and sample dilution. The RE was good for all target analytes within 84.7%-123.5% except for N-desethylacetildenafil at low (53.8%) and medium (65.1%) quality control levels. The method was successfully applied to 25 samples of ICPs where 17 of them were found to be adulterated with PDE5 inhibitors and their analogues. Further quantification revealed the total amount of these adulterants ranged from 2.77 to 121.64 mg per sachet.


Assuntos
Cromatografia Líquida/métodos , Café/química , Contaminação de Alimentos/análise , Espectrometria de Massas/métodos , Inibidores da Fosfodiesterase 5/análise , Limite de Detecção , Extração em Fase Sólida/métodos
4.
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
5.
Forensic Sci Int ; 298: 10-19, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30870700

RESUMO

The worldwide spread of illegal sexual enhancement products is posing a threat to public health. The aim of this study was to investigate illegal products claiming to be effective in improving sexual performance through the online or offline markets between 2014 and 2017; these products include foods, dietary supplements, counterfeit drugs, and herbal medicines. These samples were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the presence of 80 PDE-5 inhibitors (PDE-5i) and analogues. The developed method was validated as follows: LODs and LOQs spiked in solid- and liquid-type negative samples (0.03-3.33 ng/mL and 0.08-10.00 ng/mL), linearities (R2 > 0.997), recoveries spiked negative samples (82.2-109.3 %), accuracies (81.6-118.9 %), precisions (≥ 6.5%, RSD) of intra-day and inter-day, and stability (≥10.0%, RSD). Out of 362 measured samples, 145 were adulterated samples mostly detected in food (51%). Sildenafil group (50%) was frequently observed, followed by tadalafil group (41%). Although sildenafil and tadalafil were mainly detected in adulterated samples, their analogues were also found. In particular, new analogues have appeared steadily on illicit erectile dysfunction (ED) products even after they were first discovered. The concentration of detected samples ranged from 0.1 to 826.0 mg/g, and sildenafil of them contained a considerable amount in illicit ED products in 2014, posing a potential toxicology risk of public health. The testing method is fast and reliable making it suitable for both routine screening and up-to-date quantitative analysis of PDE-5i and their analogues in suspicious foods, dietary supplements, and counterfeit drugs.


Assuntos
Comércio , Medicamentos Falsificados , Inibidores da Fosfodiesterase 5/análise , Cromatografia Líquida , Suplementos Nutricionais , Formas de Dosagem , Contaminação de Alimentos/análise , Humanos , Internet , Limite de Detecção , Espectrometria de Massas , Inibidores da Fosfodiesterase 5/química , Fitoterapia
6.
J Pharm Biomed Anal ; 168: 201-208, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30825803

RESUMO

The introduction of sildenafil (SDF) to treat erectile dysfunction has solved a widespread condition with negative on the quality of life. Recently, the co-administration of tramadol (TMD) with SDF to manage premature ejaculation has illegally increased and thus drug-drug interaction studies of these drugs became of great importance. Although certain biological functions have been altered upon co-administration of the two drugs, methods for their determination in vivo to understand their interactions have yet to be published. Herein, therefore, an HPLC method with photometric detection was developed for the determination of a binary mixture of TMD and SDF in rabbit plasma after oral administration. In this study, a reversed-phase chromatography was performed at room temperature on a C18 column with a mobile phase composed of 10 mM Na2HPO4 solution (pH 7.5): acetonitrile (45:55, v/v) at a flow rate of 0.8 mL min-1 using caffeine (CAF) as an internal standard. The detector was set at 220 nm. The total analysis time was 6 min. Calibration graphs were linear in the concentration ranges of 0.1-10 and 0.05-10 µg mL-1 with a detection limit of 0.05 and 0.02 µg mL-1 for TMD and SDF, respectively. The method was validated in terms of accuracy, precision, limit of detection and quantitation, recovery, and stability as per US FDA bioanalytical guidelines. In addition, the metabolites N-desmethylsildenafil (UK-103,320) and O-desmethyltramadol were quantified in rabbit plasma after 2 h of oral administration using LC-MS/MS. The simultaneous administration of TMD with SDF has affected peak plasma concentration (Cmax), Tmax, area under the concentration-time curve (AUC), and the elimination rate constant (Kel) of SDF. The present study is the first to give valuable insights into the drug-drug interaction and the pharmacokinetic implications associated with the co-administration of SDF and TMD.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Citrato de Sildenafila/análise , Espectrometria de Massas em Tandem/métodos , Tramadol/análise , Administração Oral , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/análise , Analgésicos Opioides/farmacocinética , Animais , Calibragem , Cromatografia de Fase Reversa/métodos , Interações Medicamentosas , Quimioterapia Combinada , Limite de Detecção , Masculino , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/análise , Inibidores da Fosfodiesterase 5/farmacocinética , Coelhos , Reprodutibilidade dos Testes , Citrato de Sildenafila/administração & dosagem , Citrato de Sildenafila/farmacocinética , Tramadol/administração & dosagem , Tramadol/análogos & derivados , Tramadol/farmacocinética
7.
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
8.
Talanta ; 195: 870-875, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30625631

RESUMO

The practice of drug counterfeiting is an important challenge due to the extremely rapid growth rate of this disturbing trend and its immense potential harmfulness. According to WHO even 10% of counterfeit medicines can be exact copies of genuine medicines: they have exactly the same quantitative and qualitative composition in terms of both API and excipients. Thus, the identification of such drugs using chemical analysis methods can be very difficult or even impossible. The aim of this study was to verify the effectiveness of using computed microtomography in the identification of counterfeit medicines. The General Electric v|tome|x s microtomography system was used in the study. The recorded microtomographic scans were subjected to analysis and image processing. The following parameters of image analysis and processing were identified: mean brightness, homogeneity, contrast, quadratic tree decomposition. The original and falsified 100-mg Viagra® tablets (Pfizer) were compared. 8 original Viagra® tablets (hereinafter referred to as T) and 8 falsified tablets (hereinafter referred to as F1-F8) were tested. The range of variation for the genuine medicines against fake products was: brightness: 90.9-117.1 vs 33.8, 50.1, homogeneity: 0.84-0.92 vs 0.94-1.01 and quadratic tree decomposition for the 1 × 1 mask: 55768-58792 vs 0-439. The proposed method of microtomographic image analysis and processing enables to identify solid dosage forms, including those that are an accurate chemical copy, with high sensitivity and specificity, 94.5% and 97%, respectively. The advantage of the µCT method is its high efficiency and speed, whereas the disadvantages include the possibility of using only solid dosage forms and high equipment costs.


Assuntos
Medicamentos Falsificados/análise , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Microtomografia por Raio-X
9.
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
10.
J Pharm Biomed Anal ; 164: 713-724, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30472590

RESUMO

Popularity of natural-based preparations supporting the sexual potency significantly increased in recent years, which also led to the increase of illegal use of phosphodiesterase type 5 inhibitor (PDE-5) in sexual performance enhancement products. In this study, a rapid U-HPLC‒HRMS/MS method has been developed to simultaneously determine 59 PDE-5 inhibitors and their analogues. Within the development of sensitive method for analysis of 59 PDE-5 inhibitors and their analogues, both sample preparation procedure, as well as separation / detection conditions have been optimized. Extraction efficiency of particular extraction solvents, influence of different mobile phase additives on target analytes separation, as well as impact of various settings of mass analyzer on sensitivity of detection were examined. Data were collected in the 'full MS/data dependent MS/MS' acquisition mode (full MS-dd-MS/MS). Before the U-HPLC‒HRMS/MS method was used for analysis of real samples, proper validation had been conducted. The precision of the method expressed as the relative standard deviation (RSD) was ≤4.2% and ≤5.2% at spiking concentrations 5 µg/g and 0.25 µg/g, respectively. The limits of quantification were in the range 0.25 - 0.05 µg/g and the recovery ranged between 71 and 90%. The optimized method was successfully applied for analysis of 64 real samples, and 10 of them were proved to contain both registered or unregistered synthetic PDE-5 inhibitors. Additionally, the acquired U-HPLC‒HRMS/MS fingerprints were demonstrated to serve as an efficient tool for revealing of other type of possible fraud in products labeling. Retrospective mining of markers of herbs declared on dietary supplements packaging allowed to assess the trueness / untruth in the declaration of medical herbs composition.


Assuntos
Medicamentos Falsificados/análise , Suplementos Nutricionais/normas , Fraude/prevenção & controle , Inibidores da Fosfodiesterase 5/análise , Compostos Fitoquímicos/normas , Cromatografia Líquida de Alta Pressão/métodos , República Tcheca , Suplementos Nutricionais/análise , Contaminação de Medicamentos/prevenção & controle , Limite de Detecção , Compostos Fitoquímicos/análise , Espectrometria de Massas em Tandem/métodos
11.
Se Pu ; 36(10): 1005-1017, 2018 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-30378360

RESUMO

The presence of illegally adulterated sildenafil and related compounds in dietary supplements was qualitatively analyzed by employing ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Samples were extracted by ultrasonic method using methanol. The analysis was performed on an Agilent Poroshell 120 SB-C18 column (75 mm×3.0 mm, 2.7 µm) using gradient elution with a mixture of aqueous formic acid solution (0.1%, v/v) and acetonitrile as the mobile phase at a flow rate of 0.4 mL/min. Q-TOF-MS equipped with ESI ion source was operated in a positive ionization mode. Qualitative analysis was based on the retention time and the accurate relative molecular mass of elemental compositions of the precursor ion and product ions. The limits of detection (LODs) of sildenafil and other 99 compounds were found to be 0.1-50 mg/kg or 0.1~50 mg/L in 10 different matrices. In this manuscript, the fragmentation behavior of 98 phosphodiesterase-5 inhibitors are categorically summarized, which can provide information for referencing and identification of suspicious compounds. The method was successfully applied to the analysis of actual samples, of which 19 compounds combated the illegal adulteration behavior effectively.


Assuntos
Cromatografia Líquida de Alta Pressão , Suplementos Nutricionais/análise , Contaminação de Medicamentos , Espectrometria de Massas , Citrato de Sildenafila/análise , Limite de Detecção , Inibidores da Fosfodiesterase 5/análise
12.
Anal Chem ; 90(18): 10765-10770, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30148354

RESUMO

A novel "Prediction and Confirmation" (PC) strategy was proposed for characterizing phosphodiesterase-5 inhibitor (PDE-5) derivatives in botanical dietary supplements (BDSs) for on-site detection. Discovery Studio (DS) and density functional theory (DFT) calculations were used for the "Prediction" step in order to estimate PDE-5 derivative structures and theoretical Raman shifts without synthesizing the derivatives. After 11 potentially bioactive sildenafil derivatives were acquired through DS, 32 common calculated Raman shifts were obtained through DFT. The mean absolute wavenumber deviation (δ, peak range) of the major bands and the minimum number (τ) of Raman spectral peaks matching the calculated common shifts were optimized, so that a positive result of an unknown sample could be reasonably produced. In this study, δ was set at ±10 cm-1 and the corresponding τ was set at 4-5 after optimization. Surface plasmon resonance (SPR) biosensor and surface-enhanced Raman scattering (SERS) detection were the "Confirmation" step to validate the reliability and accuracy of DS and DFT in the "Prediction" step, respectively. The optimized δ and τ criteria were used as indexes for on-site SERS detection after thin-layer chromatographic (TLC) separation of six real-world samples, one of which was preliminarily identified as "suspected positive samples." This strategy allows for a quick determination of the BDSs adulterated with sildenafil or its derivatives, independent of any standard materials.


Assuntos
Suplementos Nutricionais/análise , Modelos Teóricos , Inibidores da Fosfodiesterase 5/análise , Extratos Vegetais/química , Citrato de Sildenafila/análise , Técnicas Biossensoriais , Cromatografia em Camada Delgada , Teoria da Densidade Funcional , Simulação de Acoplamento Molecular , Inibidores da Fosfodiesterase 5/normas , Padrões de Referência , Citrato de Sildenafila/normas , Análise Espectral Raman , Ressonância de Plasmônio de Superfície/métodos
13.
J Pharm Biomed Anal ; 161: 61-65, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30145450

RESUMO

A new sildenafil analog has been identified in the softgel shell of a dietary supplement. The compound was investigated by UV spectroscopy and high-resolution MS analysis, leading to the proposed structure 1-methyl-5-{5-[2-(4-methylpiperazin-1-yl)acetyl]-2-propoxyphenyl}-3-propyl-1,6-dihydro-7H-pyrazolo[4,3-d]pyrimidin-7-one. A synthetic reference compound with the proposed structure was prepared, and the two sets of analytical data were compared, confirming the structure of the new compound. The compound was named propoxyphenyl noracetildenafil from its structure and similarity with the known compound.


Assuntos
Suplementos Nutricionais/análise , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análogos & derivados , Cromatografia Líquida de Alta Pressão , Drogas Ilícitas/análise , Drogas Ilícitas/síntese química , Drogas Ilícitas/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Inibidores da Fosfodiesterase 5/síntese química
14.
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
15.
Food Addit Contam Part B Surveill ; 11(3): 214-222, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29909756

RESUMO

Chinese tonic liquor is an important dietary supplement in daily use, but it often happens that illicitly adulterated drugs in Chinese tonic liquor could lead to food safety issues. In this survey, an analytical method consisting of a liquid chromatography-quadrupole-time of flight mass spectrometer (LC-Q-TOF-MS), coupled with quick easy cheap effective rugged safe (QuEChERS) pretreatment, was established for identification of phosphodiesterase type 5 enzyme (PDE-5) inhibitors in Chinese tonic liquors. 86 PDE-5 inhibitors were qualitatively analysed by employing information dependent acquisition mass spectrometry (IDA-MS) in comparison with the accurate mass of the protonated molecular ion, isotopic pattern, library and chemical formula. This method was used to test 28 Chinese tonic liquor samples. The results revealed that the IDA-MS screening method is suitable for qualitative analysis of 86 PDE-5 inhibitors. Four samples were found to be adulterated with sildenafil, tadalafil, vardenafil, isopiperazinoafil, nortadalafil and desmethylsidenafil, which was 14.3% of the tested samples.


Assuntos
Bebidas Alcoólicas/análise , Suplementos Nutricionais/análise , Contaminação de Alimentos , Inibidores da Fosfodiesterase 5/análise , Calibragem , China , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Biologia Computacional , Bases de Dados de Produtos Farmacêuticos , Inspeção de Alimentos , Humanos , Isomerismo , Limite de Detecção , Estrutura Molecular , Peso Molecular , Inibidores da Fosfodiesterase 5/química , Bibliotecas de Moléculas Pequenas , Espectrometria de Massas em Tandem
16.
Environ Int ; 115: 279-284, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29621715

RESUMO

In this work a step forward in investigating the use of prescription drugs, namely erectile dysfunction products, at European level was taken by applying the wastewater-based epidemiology approach. 24-h composite samples of untreated wastewater were collected at the entrance of eight wastewater treatment plants serving the catchment within the cities of Bristol, Brussels, Castellón, Copenhagen, Milan, Oslo, Utrecht and Zurich. A validated analytical procedure with direct injection of filtered aliquots by liquid chromatography-tandem mass spectrometry was applied. The target list included the three active pharmaceutical ingredients (sildenafil, tadalafil and vardenafil) together with (bio)transformation products and other analogues. Only sildenafil and its two human urinary metabolites desmethyl- and desethylsildenafil were detected in the samples with concentrations reaching 60 ng L-1. The concentrations were transformed into normalized measured loads and the estimated actual consumption of sildenafil was back-calculated from these loads. In addition, national prescription data from five countries was gathered in the form of the number of prescribed daily doses and transformed into predicted loads for comparison. This comparison resulted in the evidence of a different spatial trend across Europe. In Utrecht and Brussels, prescription data could only partly explain the total amount found in wastewater; whereas in Bristol, the comparison was in agreement; and in Milan and Oslo a lower amount was found in wastewater than expected from the prescription data. This study illustrates the potential of wastewater-based epidemiology to investigate the use of counterfeit medication and rogue online pharmacy sales.


Assuntos
Inibidores da Fosfodiesterase 5/análise , Águas Residuárias/química , Poluentes Químicos da Água/análise , Cidades , Europa (Continente) , Humanos
17.
Curr Drug Saf ; 13(1): 12-20, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29359677

RESUMO

INTRODUCTION: Due to the chaos in the legislation in the Middle East, male enhancement nutraceuticals may be sold without any registration or evaluation. These products need to be evaluated with respect to safety and efficacy. Furthermore, cultural and social considerations in the Middle East prevent the use of international evaluations schemes for erectile dysfunction. AIM: Evaluating the safety and efficacy parameters of generic and nutraceutical products for erectile dysfunction in the Middle East through a custom-designed, representable and simple system tailored to the regional culture. METHODS: 74 healthy male volunteers were enrolled into a comparative, simple randomized, single dose, double blind, and crossover clinical study incorporated with a tailored-designed questionnaire. Safety assessment included laboratory analysis for liver functions and measuring blood pressure. MAIN OUTCOME MEASURES: Subjective data regarding safety and efficacy were assessed from the validated questionnaire. Blood pressure was measured. Blood samples were collected to assess the drug/adulterants concentration and liver and kidney functions. RESULTS: All tested nutraceuticals showed undeclared Sildenafil citrate in patients. Questionnaire results showed high inter-patient variability with respect to efficacy and comparable safety profile compared to Viagra®. CONCLUSION: The validated tailored-designed questionnaire effectively assessed the efficacy and safety of male enhancement products. The male enhancement nutraceuticals, sold in Egypt, claimed to be 100% natural are adulterated and of questionable safety profile.


Assuntos
Suplementos Nutricionais/análise , Contaminação de Medicamentos , Medicamentos Genéricos/análise , Disfunção Erétil/sangue , Disfunção Erétil/epidemiologia , Citrato de Sildenafila/análise , Adulto , Estudos Cross-Over , Método Duplo-Cego , Contaminação de Medicamentos/prevenção & controle , Medicamentos Genéricos/metabolismo , Medicamentos Genéricos/uso terapêutico , Egito/epidemiologia , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Fosfodiesterase 5/análise , Inibidores da Fosfodiesterase 5/sangue , Inibidores da Fosfodiesterase 5/uso terapêutico , Citrato de Sildenafila/sangue , Citrato de Sildenafila/uso terapêutico , Resultado do Tratamento
18.
J Pharm Biomed Anal ; 149: 586-590, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29197805

RESUMO

Recently, illegal sildenafil analogues have emerged, causing serious social issues. In spite of the importance of sildenafil analogues, their metabolic profiles or clinical effects have not been reported yet. In this study, new metabolites of illegal sildenafil analogues such as hongdenafil, homosildenafil, and hydroxyhomosildenafil were determined using liquid chromatography quadrupole-time of flight mass spectrometry (LC-Q-TOF-MS) and tandem mass spectrometry (LC-Q-TOF-MS/MS). To prepare metabolic samples, in vitro and in vivo studies were performed. For in vivo metabolites analysis, urine and feces samples of rats treated with sildenafil analogues were analyzed. For in vitro metabolites analysis, human liver microsomes incubated with sildenafil analogues were extracted and analyzed. All metabolites were characterized by LC-Q-TOF-MS and LC-Q-TOF-MS/MS. As a result, five, six, and seven metabolites were determined in hongdenafil, homosildenafil, and hydroxyhomosildenafil treated samples, respectively. These results could be applied to forensic science and other analytical fields. Moreover, these newly identified metabolites could be used as fundamental data to determine the side effect and toxicity of illegal sildenafil analogues.


Assuntos
Medicamentos Falsificados/análise , Toxicologia Forense/métodos , Inibidores da Fosfodiesterase 5/análise , Citrato de Sildenafila/análise , Agentes Urológicos/análise , Animais , Química Farmacêutica , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos Falsificados/química , Medicamentos Falsificados/metabolismo , Medicamentos Falsificados/toxicidade , Humanos , Masculino , Microssomos Hepáticos/metabolismo , Inibidores da Fosfodiesterase 5/química , Inibidores da Fosfodiesterase 5/metabolismo , Inibidores da Fosfodiesterase 5/toxicidade , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Citrato de Sildenafila/análogos & derivados , Citrato de Sildenafila/metabolismo , Citrato de Sildenafila/toxicidade , Espectrometria de Massas em Tandem/métodos , Agentes Urológicos/química , Agentes Urológicos/metabolismo , Agentes Urológicos/toxicidade
19.
Talanta ; 174: 638-644, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28738634

RESUMO

High-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS2) with a triple quadrupole is proposed for determining the synthetic phosphodiesterase-5 inhibitors, sildenafil, tadalafil and vardenafil, and the active metabolite N-desmethyl sildenafil. The method was successfully applied to the analysis of waters of different origins and human urine samples. Dispersive liquid-liquid microextraction (DLLME) was applied in the classical way for water analysis, whereas a previous extraction into an organic solvent was necessary for urine samples, the acetonitrile extract being used as dispersant solvent in the DLLME step. The analytes were determined by LC-ESI-MS2 in the multiple reaction monitoring mode. Detection limits were in the 5-50 and 15-250ngL-1 ranges for water and urine samples, respectively. The repeatability was calculated using the relative standard deviation, obtaining values of between 3.6% and 10.1%. The enrichment factors were between 75 and 81. Accuracy of the procedure was calculated through recovery assays and average recoveries ± SD (n = 48) of 93.6 ± 3.5 and 91.1 ± 3.5 were obtained for water and urine samples, respectively. None of the samples analyzed contained the target compounds, at least above the corresponding detection limits.


Assuntos
Microextração em Fase Líquida , Inibidores da Fosfodiesterase 5/análise , Inibidores da Fosfodiesterase 5/urina , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/urina , Água/química , Cromatografia Líquida , Humanos , Limite de Detecção , Espectrometria de Massas , Inibidores da Fosfodiesterase 5/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação
20.
Artigo em Inglês | MEDLINE | ID: mdl-28580889

RESUMO

Adulteration of herbal health supplements with phosphodiesterase-5 (PDE-5) inhibitors and their analogues is becoming a worldwide problem. The aim of this study was to investigate herbal and food products sold in the Malaysian market for the presence of these adulterants. Sixty-two products that claim to enhance men's sexual health were sampled between April 2014 and April 2016. These products included unregistered products seized by the Pharmacy Enforcement Division of the Ministry of Health (n = 39), products sent to the National Pharmaceutical Regulatory Agency for pre-registration testing (n = 9) and products investigated under the post-registration market surveillance programme (n = 14). The products were tested against an in-house spectral library consisting of 61 PDE-5 inhibitors and analogues using a validated liquid chromatography-mass spectrometry ion-trap-time-of-flight (LC-MS IT-TOF) method. Thirty-two (82%) of the unregistered products and two (14%) of the registered products were found to be adulterated with at least one PDE-5 inhibitor or analogue, while none of the pre-registration products contained adulterants. A total of 16 different adulterants were detected and 36% of the adulterated products contained a mixture of two or more adulterants. This study has demonstrated that the adulteration of unregistered herbal products in the Malaysian market is an alarming issue that needs to be urgently addressed by the relevant authorities.


Assuntos
Contaminação de Medicamentos , Contaminação de Alimentos/análise , Inibidores da Fosfodiesterase 5/análise , Inibidores da Fosfodiesterase 5/química , Humanos , Malásia
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