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1.
J Chromatogr Sci ; 60(7): 671-677, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34522954

RESUMO

Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min-1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.


Assuntos
Antivirais , Inibidores de Proteases , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Excipientes , Humanos , Reprodutibilidade dos Testes , Comprimidos
2.
Biopharm Drug Dispos ; 42(1): 3-11, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33119133

RESUMO

Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder (ADHD) and binge-eating disorder (BED) symptoms. In vivo hydrolysis of the LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). This study aims to describe the pharmacokinetics of LDX and its major metabolite d-AMPH in human oral fluid, urine and plasma after a single 70 mg oral dose of LDX dimesylate. Six volunteers participated in the study. Oral fluid and blood samples were collected for up to 72 h and urine for up to 120 h post-drug administration for the pharmacokinetic evaluation of intact LDX and d-AMPH. Samples were analyzed by LC-MS/MS. Regarding noncompartmental analysis, d-AMPH reached the maximum concentration at 3.8 and 4 h post-administration in plasma and oral fluid, respectively, with a mean peak concentration value almost six-fold higher in oral fluid. LDX reached maximum concentration at 1.2 and 1.8 h post-administration in plasma and oral fluid, respectively, with a mean peak concentration value almost three-fold higher in plasma. Intact LDX and d-AMPH were detected in the three matrices. The best fit of compartmental analysis was found in the one-compartment model for both analytes in plasma and oral fluid. There was a correlation between oral fluid and plasma d-AMPH concentrations and between parent to metabolite concentration ratios over time in plasma as well as in oral fluid.


Assuntos
Anfetamina/farmacocinética , Dimesilato de Lisdexanfetamina/farmacocinética , Saliva/metabolismo , Administração Oral , Adulto , Cromatografia Líquida , Humanos , Dimesilato de Lisdexanfetamina/administração & dosagem , Masculino , Espectrometria de Massas em Tandem , Adulto Jovem
3.
Clin Transplant ; 34(8): e13997, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32484985

RESUMO

Immunosuppressive therapy is used in solid organ transplant treatment, and mycophenolic acid (MPA) is one of the immunosuppressive drugs most used worldwide. It is a potent, selective, non-competitive, and reversible inosine monophosphate dehydrogenase (IMPDH) inhibitor that acts to inhibit guanine synthesis. To improve solubility, MPA is used as the prodrug mycophenolate mofetil (MMF) or as an enteric-coated mycophenolate sodium salt (EC-MPS). It is metabolized into mycophenolic acid phenyl glucuronide (MPAG), the inactive and major metabolite, and into acyl glucuronide (AcMPAG), pharmacologically active. In kidney transplantation, combined immunosuppressive therapy with cyclosporine (CsA) and tacrolimus (Tac) is widely used, showing beneficial effects. This paper aimed to review papers published in the last two decades and discuss factors that can interfere with the pharmacokinetics of MPA. Data collected confirm that MPA plasma levels should be monitored to evaluate immunosuppressive therapy since pharmacokinetics can be influenced by factors such as interpatient variability, coadministration of other immunosuppressive agents, post-transplant period, renal function, and dose. However, to perform drug monitoring, costs and facility may be limitations. Monitoring MPAG together with MPA would be a great improvement in therapy as it represents a big part of MPA levels and can be related to the increase of adverse effects.


Assuntos
Transplante de Rim , Ácido Micofenólico , Ciclosporina , Humanos , Imunossupressores , Tacrolimo
4.
Metabolomics ; 16(2): 16, 2020 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955274

RESUMO

INTRODUCTION: Canis lupus familiaris is a domestic dog and many owners consider their pets as a family member. Medical bills with dogs are overcame only by the health care received by humans. Medical care is constantly progressing, and so is veterinary care. Metabolomics is the ''omic" technique aimed to the study of metabolome, low-molecular weight molecules, through biofluids or tissue samples. And it also allows to evaluate disease diagnosis and prognosis, therapeutic evaluation and toxicological studies. OBJECTIVES: The goal of this paper is to review the current and potential applications of metabolomics in domestic dogs. METHOD: ScienceDirect, Scopus, Reaxys and PubMed were searched for papers that performed canine metabolomics in any research area. RESULTS: We analysed 38 papers, published until April 2019 in canine metabolomics approach. Metabolomic research in dogs so far can be divided into three areas: (a) Metabolomics studies in veterinary science, such as improving pet dogs health and welfare. (b) Diet, breeds and species discrimination. (c) Use of dogs as animal model in different diseases and drug development (evaluation toxicity and effect). CONCLUSIONS: The results of this review showed that interest in metabolomics is growing in veterinary research. Several canine diseases have been evaluated with some promise for potential biomarker and/or disease mechanism discovery. Because canine metabolomics is a relatively new area, the researches spread across different research areas and with few studies in each area.


Assuntos
Cães/metabolismo , Metabolômica , Animais
5.
Eur J Clin Pharmacol ; 75(4): 553-559, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30610275

RESUMO

PURPOSE: Mycophenolic acid is one of the most used immunosuppressive drugs in solid organ transplant treatments in the world. Developing a highly sensitive analytical method to analyse the drug and its metabolites in oral fluid and plasma is important to evaluate the possibility of using oral fluid as a biological matrix in therapeutic drug monitoring, instead of plasma. METHOD: The liquid chromatography coupled to mass spectrometry (LC-MS) method was developed and validated for determining mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in oral fluid and plasma, with both matrices presenting a detection limit of 1 ng/mL for MPA and 5 ng/mL for MPAG. Both analytes were analysed after a simple protein precipitation procedure. Transplanted-kidney samples of oral fluid and blood were collected from 13 patients that were hospitalised and kept at - 80 °C until analyses. RESULTS: The proposed method was linear in the concentration range of 5-500 ng/mL for MPA and 10-500 ng/mL for MPAG, with correlation coefficients (r) between 0.9925 and 0.9973. It was then applied to samples collected from kidney-transplanted patients and used for calculation of pharmacokinetics parameters. CONCLUSION: After comparing plasma and oral fluid concentrations as well as performing a non-compartmental pharmacokinetic analysis of the average curves, it is possible to suggest that oral fluid concentration may be used as an alternative for MPA and MPAG monitoring in kidney transplant patients.


Assuntos
Glucuronídeos/metabolismo , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/farmacocinética , Saliva/metabolismo , Cromatografia Líquida/métodos , Glucuronídeos/análise , Glucuronídeos/sangue , Glucuronídeos/farmacocinética , Humanos , Ácido Micofenólico/análise , Ácido Micofenólico/sangue , Espectrometria de Massas em Tandem/métodos
6.
Drug Dev Ind Pharm ; 45(1): 139-146, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30231652

RESUMO

Lisdexamfetamine dimesylate (LDX), a long-acting prodrug stimulant indicated for the treatment of the attention-deficit/hyperactivity disorder (ADHD), was subjected to forced degradation studies by acid and alkaline hydrolysis and the degradation profile was studied. To obtain between 10-30% of degraded product, acid and alkaline conditions were assessed with solutions of 0.01 M, 0.1 M, 0.5 M, and 1 M of DCl and NaOD. These solutions were analyzed through 1 H NMR spectra. Acid hydrolysis produced no degradation in 0.01 M and 0.1 M DCl and 4.38%, 9.69%, and 17.75% of degradation LDX, respectively, in 0.5 M, 1 M (4h) and 1 M (4 + 12 h) DCl. And alkaline hydrolysis produced no degradation in 0.01 M and 0.1 M DCl and a degradation LDX extension of 8.5%, 14.30%, and 22.91%, respectively, in 0.5 M, 1 M (4h) and 1 M (4 + 12 h) NaOD. LDX solutions subjected to 1 M (4 + 12 h) acid and alkaline hydrolysis were evaluated by NMR spectra (1 H NMR, 13 C NMR, HSQC and HMBC). LDX degradation product (DP) was identified and its structure elucidated as a diastereoisomer of LDX: (2R)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl] hexanamide without their physical separation.


Assuntos
Estimulantes do Sistema Nervoso Central/análise , Estimulantes do Sistema Nervoso Central/metabolismo , Dimesilato de Lisdexanfetamina/análise , Dimesilato de Lisdexanfetamina/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Estabilidade de Medicamentos
7.
J Pharmacol Toxicol Methods ; 86: 60-66, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28395991

RESUMO

INTRODUCTION: A single LC-MS equipment was used to validate three methods for simultaneously analyzing cocaine (COC), benzoylecgonine (BZE), cocaethylene (CE), anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) in oral fluid (OF), urine and plasma. METHODS: The methods were carried out using a Kinetex HILIC column for polar compounds at 30°C. Mobile phase with isocratic condition of acetonitrile: 13mM ammonium acetate pH 6.0: methanol (55:35:10 v/v/v) at 0.8mL/min flow rate was used. RESULTS: After buffer dilution (OF) and protein precipitation (urine and plasma), calibration curve ranges were 4.25-544ng/mL for oral fluid and 5-320ng/mL for urine and plasma with correlation coefficients (r) between 0.9947 and 0.9992. The lowest concentration of the calibration curves were the lower limit of quantification. No major matrix effect could be noted, demonstrating the efficiency of the cleaning procedure. DISCUSSION: The methods were fully validated and proved to be suitable for analysis of 124 cocaine and/or crack cocaine users. Among the subjects, 56.5% reported daily use of cocaine in the previous three months. Results show a high prevalence of the analytes, with BZE as the most prevalent (94 cases), followed by COC (93 cases), AEC (70 cases), CE (33 cases) and AEME (13 cases). In addition, the concentration of BZE in urine was higher compared to OF and plasma found in the real samples, showing the facility of accumulation in chronic users in matrices with a large detection window.


Assuntos
Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Cocaína/análise , Cocaína Crack/análise , Detecção do Abuso de Substâncias/métodos , Adolescente , Adulto , Calibragem , Cromatografia Líquida de Alta Pressão , Humanos , Limite de Detecção , Espectrometria de Massas , Padrões de Referência , Reprodutibilidade dos Testes , Saliva/química , Sensibilidade e Especificidade , Extração em Fase Sólida , Adulto Jovem
8.
J AOAC Int ; 100(2): 400-405, 2017 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-28118563

RESUMO

Stability-indicating LC methods using a UV detector and a charged aerosol detector (CAD) simultaneously were validated for the assessment of alogliptin (ALG) in tablets. The analysis was performed on a C8 column (250 × 4.6 mm, 5 µm) at a flow of 0.8 mL/min, using acetonitrile-10 mM ammonium acetate buffer (pH 3.5; 90 + 10, v/v) as mobile phase and UV detection at 275 nm. Validation followed the International Conference on Harmonization guidelines. The method was linear over the range of 25-200 µg/mL. Normality of the residuals showed a normal distribution, no autocorrelation, and homoscedasticity. LODs were 6.25 and 2.65 µg/mL and LOQs were 20.85 and 8.84 µg/mL for the CAD and the UV detector, respectively. The methods were precise and accurate. Excipients and degradation products did not interfere in the methods in studies of specificity. None of the factors studied in the analysis of robustness had a significant effect on the quantification of the ALG by the Pareto chart. The results of the assay obtained with LC-CAD and LC-UV were similar. The methods could be considered interchangeable and stability-indicating, and can be applied as an appropriate QC tool for analysis of ALG in tablets.


Assuntos
Piperidinas/análise , Uracila/análogos & derivados , Ácido Benzoico/análise , Cromatografia Líquida , Estabilidade de Medicamentos , Excipientes/análise , Limite de Detecção , Manitol/análise , Piperidinas/administração & dosagem , Comprimidos , Uracila/administração & dosagem , Uracila/análise
9.
Biomed Chromatogr ; 31(3)2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27518755

RESUMO

Lisdexamfetamine (LDX) is a long-acting prodrug stimulant indicated for the treatment of attention-deficit/hyperactivity disorder and binge-eating disorder symptoms. In vivo hydrolysis of LDX amide bond releases the therapeutically active d-amphetamine (d-AMPH). Since toxicological tests in biological samples can detect AMPH from the use of some legal medications, efficient methods are needed in order to correctly interpret the results. The aim of this study was to develop and validate an LC-MS/MS method for the simultaneous quantification of LDX and its main biotransformation product AMPH in human oral fluid, plasma and urine. Calibration curve range for both analytes was 1-128 ng/mL in oral fluid and plasma and 4-256 ng/mL in urine, being the lowest concentration the limit of quantification. Accuracy of the determined values of the target analytes for the five control levels ranged from 94.8 to 111.7% for oral fluid, from 91.3 to 100.2% for plasma and from 94.8 to 109.8% for urine. Imprecision for the five control levels did not exceeded 12.8% for oral fluid, 16.2% for plasma and 17.1% for urine. The method developed for the three matrices was validated and was also successfully applied to assess real samples, showing for the first time the detection of LDX in oral fluid.


Assuntos
Anfetamina/análise , Cromatografia Líquida , Testes de Química Clínica/métodos , Dimesilato de Lisdexanfetamina/análise , Espectrometria de Massas em Tandem , Anfetamina/sangue , Anfetamina/urina , Testes de Química Clínica/normas , Humanos , Dimesilato de Lisdexanfetamina/sangue , Dimesilato de Lisdexanfetamina/urina , Reprodutibilidade dos Testes , Saliva/química
10.
Eur J Clin Pharmacol ; 72(8): 945-51, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27066959

RESUMO

PURPOSE: There are no pharmacokinetics studies in oral fluid reported in the literature, as well as there are no data on correlation of drug levels in plasma, urine, and oral fluid in order to propose alternative matrices to monitor the use of mazindol by drivers. The present work aimed to study, preliminarily, mazindol's pharmacokinetics in plasma and oral fluid, as well as investigate the correlation of drug levels in urine, plasma, and oral fluid. METHOD: Blood, urine, and oral fluid samples from seven healthy male volunteers were collected at 0, 1, 2, 4, 5, 6, 8, 10, and 24 h after administration of tablets of 2 mg mazindol and analyzed by a previously validated method by LC-MS with liquid-liquid extraction. Levels of the drug found were higher in plasma when compared with oral fluid and higher in urine in relation to plasma. The study of the mazindol's pharmacokinetics showed that the most suitable model to describe the variation of the concentration over time is the compartment open model with absorption and elimination following the first-order kinetics, and confirming literature data, drug is metabolized, being the major metabolite detected, but not quantified. CONCLUSION: It was not found a good correlation between the concentrations of mazindol in urine and plasma, but between plasma and oral fluid, there was a good correlation, suggesting this as an alternative matrix to plasma. However, studies involving more subjects are needed.


Assuntos
Estimulantes do Sistema Nervoso Central/farmacocinética , Mazindol/farmacocinética , Administração Oral , Adulto , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Voluntários Saudáveis , Humanos , Masculino , Mazindol/sangue , Mazindol/urina , Modelos Biológicos , Saliva/química , Adulto Jovem
11.
Eur J Pharm Sci ; 89: 172-9, 2016 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-27125257

RESUMO

Lisdexamfetamine (LDX) is a d-amphetamine (d-AMPH) pro-drug used to treat Attention Deficit and Hyperactivity Disorder (ADHD) and Binge Eating Disorder (BED) symptoms. The in vivo pharmacodynamics of LDX is the same as that of its active product d-AMPH, although there are a few qualitative and quantitative differences due to pharmacokinetics. Due to the specific pharmacokinetics of the long-acting stimulants, this article revises the pharmacokinetic studies on LDX, the newest amphetamine pro-drug. The Medline/Pubmed, Science Direct and Biblioteca Virtual em Saúde (Lilacs and Ibecs) (2007-2016) databases were searched for articles and their list of references. As for basic pharmacokinetics studies, since LDX is a newly developed medication, there are few results concerning biotransformation, distribution and the use of different biological matrices for analysis. This is the first robust review on this topic, gathering data from all clinical pharmacokinetics studies available in the literature. The particular pharmacokinetics of LDX plays a major role in studying this pro-drug, since this knowledge was essential to understand some reports on clinical effects in literature, e.g. the small likelihood of reducing the effect by interactions, the effect of long duration use and the still questionable reduction of the potential for abuse. In general the already well-known pharmacokinetic properties of amphetamine make LDX relatively predictable, simplifying the use of LDX in clinical practice.


Assuntos
Dimesilato de Lisdexanfetamina/farmacocinética , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Biotransformação/efeitos dos fármacos , Humanos , Dimesilato de Lisdexanfetamina/uso terapêutico , Pró-Fármacos/farmacocinética , Pró-Fármacos/uso terapêutico
12.
Clin Biochem ; 49(13-14): 1096-103, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26827634

RESUMO

Abusive use of drugs is a public health problem worldwide. The use of these substances by pregnant or lactating women can have many serious side effects in newborns. Among the commonest causes of addiction in drug users is cocaine in powdered form, inhaled, intravenously injected or smoked form (crack). Fast screening and a confirmation test using high specificity and sensitivity instruments such as LC-MS or GC/MS, can provide data to qualify and quantify chemical substances present in biological samples such as breast milk or meconium. Cocaine and/or crack can be detected through biomarkers or the unchanged molecule, enabling the form of cocaine use to be distinguished through the analytes. These methods must be carefully developed and validated according to internationally recognized guidelines. Thus, the study of biological matrices in which it can be detected through the development of simple and quick analytical methods can help prevent intoxication and diagnose the symptoms of dependency such as seizures, especially in babies, providing appropriate medical care.


Assuntos
Biomarcadores/análise , Transtornos Relacionados ao Uso de Cocaína/complicações , Cocaína Crack , Lactação , Espectrometria de Massas/métodos , Mecônio/química , Leite Humano/química , Cromatografia Líquida , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Feminino , Toxicologia Forense , Humanos , Gravidez
13.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1012-1013: 113-7, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26821344

RESUMO

Fetal exposure to illicit drugs is a worldwide problem, since many addicted women do not stop using it during pregnancy. Cocaine consumed in powdered (snorted or injected) or smoked (crack cocaine) form are harmful for the baby and its side effects are not completely known. Meconium, the first stool of a newborn, is a precious matrix usually discarded, that may contain amounts of substances consumed in the last two trimesters of pregnancy. Analyzing this biological matrix it is possible to detect the unaltered molecule of cocaine (COC) or its metabolite benzoylecgonine (BZE) and pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC). A liquid chromatography mass spectrometry (LC-MS) method was validated for meconium samples after solvent extraction, followed by direct injection of 10µL. Linearity covered a concentration range of 15 to 500ng/mg with a lower limit of quantification (LLOQ) of 15ng/mg for all analytes. Matrix effect was evaluated and showed adequate results. Detection of illicit substances usage can be crucial for the baby, since knowing that can help provide medical care as fast as possible. The method proved to be simple and fast, and was applied to 17 real meconium samples.


Assuntos
Biomarcadores/análise , Cromatografia Líquida/métodos , Cocaína Crack/análise , Espectrometria de Massas/métodos , Mecônio/química , Biomarcadores/química , Cocaína Crack/química , Humanos , Recém-Nascido , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
14.
Artigo em Inglês | MEDLINE | ID: mdl-26718151

RESUMO

INTRODUCTION: Even after removal of some stimulants, like fenproporex, amfepramone and mazindol, from Brazilian market, the use of these substances is still high, especially by drivers. Mazindol is the second most used anorectic agent in the world acting as an indirect sympathomimetic agonist, having stimulatory action on central nervous system. Plasma is a good matrix to monitor since it reflects the psychomotor effects of these drugs, but unlike urine has an invasive collection; drug levels and detection time are quite low. METHOD: The method involved a liquid-liquid extraction of the samples and a LC-MS analysis was fully validated. Method was used to analyze samples of urine and plasma collected from health volunteers in a period of 24h. Metabolite of mazindol was synthesized using alkaline conditions. RESULTS: After validation the method proved to be adequate to analyze samples collected from health volunteers. Method was linear in the concentration range of 0.1-10ng/mL (r=0.9982) for plasma and 5-50ng/mL (r=0.9973) for urine. DISCUSSION: Analysis of the samples showed that mazindol can be detected after 1h of administration and that concentration levels in urine were always higher than in plasma. Mazindol metabolite was detected only in urine.


Assuntos
Cromatografia Líquida/métodos , Mazindol/sangue , Mazindol/urina , Espectrometria de Massas por Ionização por Electrospray/métodos , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Humanos , Extração Líquido-Líquido/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
15.
J Pharm Biomed Anal ; 103: 67-72, 2015 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-25462122

RESUMO

Drug abuse by nursing mothers is an ongoing concern because it may cause many adverse effects to the newborns. The development of analytical methods to analyze drugs of abuse in colostrum (first milk produced after birth) has a huge importance, because it enables the monitoring and the correct follow-up to users and newborns. A liquid chromatography mass spectrometry (LC-MS) method was developed and validated for the determination of cocaine and smoked cocaine (crack) biomarkers in colostrum. Cocaine (COC) and its major metabolite benzoylecgonine (BZE), the pyrolytic products anhydroecgonine methyl ester (AEME) and anhydroecgonine (AEC) were analyzed after a simple protein precipitation procedure using atropine (ATP) as internal standard (IS). Applying a chemometric approach study, all peaks were chromatographically separated at isocratic condition with a Kinetex HILIC column for polar compounds, at 30°C in 12min. One ion was detected for the quantification and three ions for confirmation of each analyte. The method was linear for all analytes in the concentration range of 5-300ng/mL with correlation coefficients (r) between 0.9983 and 0.9996. The lower limit of quantification (LLOQ) was 5ng/mL with acceptable validation parameters. Matrix effect was assessed by post-extraction addition approach and showed good results, demonstrating that protein precipitation cleaning procedure is fast, reliable and demand small quantities of organic solvent. The LC-MS method is fast and cheap compared to other equipments and was also successfully applied to assess real samples of colostrum from nursing mothers who were suspect of cocaine/crack abuse.


Assuntos
Biomarcadores/metabolismo , Cromatografia/métodos , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Colostro/metabolismo , Cocaína Crack , Espectrometria de Massas/métodos , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
16.
J Anal Toxicol ; 38(7): 432-7, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25038769

RESUMO

Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs.


Assuntos
Anfetaminas/sangue , Estimulantes do Sistema Nervoso Central/sangue , Dietilpropiona/sangue , Detecção do Abuso de Substâncias/métodos , Adulto , Anfetamina/sangue , Brasil , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Limite de Detecção , Masculino , Reprodutibilidade dos Testes , Microextração em Fase Sólida
17.
Biomed Chromatogr ; 28(8): 1064-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24458547

RESUMO

Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography-mass spectrometry (LC-MS). The LC system consisted of an LC-MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2-20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers.


Assuntos
Estimulantes do Sistema Nervoso Central/análise , Cromatografia Líquida de Alta Pressão/métodos , Mazindol/análise , Saliva/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Condução de Veículo , Brasil , Estimulantes do Sistema Nervoso Central/química , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Masculino , Mazindol/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
Drug Dev Ind Pharm ; 40(4): 488-93, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23614829

RESUMO

INTRODUCTION: Lodenafil carbonate is a phosphodiesterase type 5 inhibitor used for the treatment of erectile dysfunction. Currently, there is no dissolution test reported for lodenafil carbonate and this drug is not listed in any pharmacopoeia. OBJECTIVE: The present study focused on the development and validation of a dissolution test for lodenafil carbonate tablets, using a simulated absorption profile based on in vivo data. METHODS: The appropriate conditions were determined after testing sink conditions. Different conditions as medium, surfactant concentration and rotation speed were evaluated. The percentage of dose absorbed was calculated by deconvolution, using the Wagner-Nelson method. RESULTS: According to the obtained results, the use of 0.1 M HCl + 1.5% SLS (900 mL, at 37 + 0.5 °C) as the dissolution medium, paddles at 25 rpm were considered adequate. The samples were quantified by UV spectroscopy at 295 nm and the validation was performed according to international guidelines. The method showed specificity, linearity, accuracy and precision, within the acceptable range. Kinetics of drug release was better described by the first-order model. CONCLUSION: The proposed dissolution test can be used for the routine quality control of lodenafil carbonate in tablets.


Assuntos
Carbonatos/química , Modelos Teóricos , Inibidores da Fosfodiesterase 5/química , Piperazinas/química , Pirimidinas/química , Disfunção Erétil/tratamento farmacológico , Humanos , Masculino , Sensibilidade e Especificidade , Solubilidade , Espectrofotometria Ultravioleta , Tensoativos/química , Comprimidos
19.
Forensic Sci Int ; 229(1-3): 23-6, 2013 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-23683905

RESUMO

Brazil is one of the world's highest users of anorectic drugs, mainly diethylpropione, fenproporex and sibutramine. The present work focuses on physical and chemical characteristics of 17 counterfeited capsules containing amphetamine-type stimulants (ATS) from three seizures conducted by Brazilian Federal Police. The physical profile was useful in indicating forgery, bring complementary information, but the use of this data singly was not sufficient to distinguish between authentic and counterfeited medicines. The chemical analysis revealed that the seizures capsules labeled as Desobesi-M (fenproporex 25mg), actually contained the active pharmaceutical ingrediente (API) sibutramine. The amount of this API ranged from 1/3 to 2 times the amount of drug found in commercial product, may reach twice the recommended daily dose. Multivariate analysis with application of principal component analysis on data from spectroscopy attenuated total reflectance Fourier transform infrared classified the samples according to their similarities, indicating that two seizures had common origin. This study represents the first step in the elucidation of falsification of ATS in Brazil. Considering the forensic intelligence these information are valuable in order to develop and establish a database that enables correlate samples from different locations and/or suppliers and to map the profile and trends of trafficking.

20.
J AOAC Int ; 96(1): 37-41, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23513955

RESUMO

An RP-LC method was developed and validated for the determination of dabigatran etexilate in a capsule formulation. The LC method was carried out on a Zorbax C18 column (250 x 4.6 mm id). The mobile phase consisted of acetonitrile and a solution of triethylamine 0.1%, pH 6.0 adjusted with phosphoric acid (65 + 35, v/v) at a flow rate of 1.0 mL/min. The diode array detector was set at 225 nm. The chromatographic separation was obtained with retention time of 6.31 min, and linearity was in the range of 10-70 microg/mL (R2 = 0.9991). The specificity and stability-indicating capability of the method was proven through degradation studies and showing that there was no interference from the excipients. The accuracy was 100.23%, with an RSD of 1.34%. The LOD and LOQ were 0.04 and 10 microg/mL, respectively. Moreover, method validation demonstrated acceptable results for robustness and a system suitability test. The proposed method was applied for the analysis of the capsules to ensure their therapeutic efficacy.


Assuntos
Antitrombinas/análise , Benzimidazóis/análise , Cromatografia Líquida/métodos , Piridinas/análise , Cápsulas , Dabigatrana , Limite de Detecção
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