RESUMO
This study assessed the presence of the genotoxic impurity 1-methyl-4-nitrosopiperazine (MNP) in 27 batches of rifampicin capsules obtained from 11 manufacturers in China. While they were below the temporary limit of 5â¯ppm set by the US Food and Drug Administration, the observed levels (0.33-2.36â¯ppm) exceeded the acceptable threshold of 0.16â¯ppm. Building upon preliminary findings and degradation experiments, we concluded that MNP is a by-product of the oxidative degradation of rifampicin or is introduced via oxidation or nitrosation during the synthesis process involving 1-methyl-4-aminopiperazine. The pathways of MNP formation were confirmed in this study. Furthermore, we observed that the addition of antioxidants, sealed storage, and selection of dominant crystal forms can aid in controlling MNP levels.
Assuntos
Contaminação de Medicamentos , Piperazinas , Rifampina , Rifampina/química , Rifampina/análise , Contaminação de Medicamentos/prevenção & controle , Piperazinas/química , Piperazinas/análise , Mutagênicos/química , Mutagênicos/análise , Oxirredução , Cápsulas , China , Antioxidantes/química , Antioxidantes/análiseRESUMO
BACKGROUND: The widespread use and abuse of antibiotics has resulted in the pollution of water sources with antibiotic residues, posing a threat to human health, the environment, and the economy. Therefore, a highly sensitive and selective method is required for their detection in water samples. Herein, advanced ultrasensitive electrochemical sensor platform was developed by integrating gold-silver alloy nanocoral clusters (Au-Ag-ANCCs) with functionalized multi-walled carbon nanotube-carbon paste electrode (f-MWCNT-CPE) and choline chloride (ChCl) nanocomposites for simultaneously determining the residues of antimicrobial drugs, rifampicin (RAMP) and norfloxacin (NFX), in water samples. RESULTS: The developed sensor (Au-Ag-ANCCs/f-MWCNTs-CPE/ChCl) was extensively characterized using several analytical (UV-Vis, FT-IR, XRD, SEM, and EDX) and electrochemical (EIS, CV, and SWV) techniques. It exhibited outstanding performance in a wide linear range, from 14 pM to 115 µM for RAMP, and from 0.9 nM to 200 µM for NFX, with a limit of detection (LOD, 3σ/m, S/N = 3, n = 5) and a limit of quantification (LOQ, 10σ/m, S/N = 3, n = 5) values of 2.7 pM and 8.85 pM for RAMP, and 0.14 nM and 0.47 nM for NFX, respectively. The sensor also exhibited exceptional reproducibility, stability, and resistance to interference. SIGNIFICANCE: The developed sensor was effectively utilized to determine RAMP and NFX residues in hospital wastewater, river, and tap water samples, yielding recoveries within the range of 96.8-103 % and relative standard deviations below 5 %. Generally, the proposed sensor demonstrated remarkable performance in detecting the target analytes, making it an ideal tool and the first of its kind for addressing global antibiotic residue pollutants in water sources.
Assuntos
Técnicas Eletroquímicas , Norfloxacino , Rifampina , Poluentes Químicos da Água , Norfloxacino/análise , Poluentes Químicos da Água/análise , Rifampina/análise , Eletrodos , Limite de Detecção , Antibacterianos/análise , Nanotubos de Carbono/químicaRESUMO
A fluorescent sensing material based on the ternary core-shell quantum dots with outstanding optical properties and a bio-inspired molecularly imprinted polymer (MIP) as a recognition element has been prepared for selective detection of rifampicin (RFP). Firstly, AgInS2/ZnS core/shell quantum dots (ZAIS QDs) were prepared by a hydrothermal process. Then, the fluorescent sensor was prepared by coating these QDs by a dopamine-based MIP layer. The fluorescence of MIP@ZAIS QDs was quenched by RFP probably due to the photoinduced electron transfer process. The quenching constant was much higher for MIP@ZAIS QDs than the non-imprinted polymer@QDs, indicating that MIP@ZAIS QDs could selectively recognize RFP. Under the optimized conditions, the sensor had a good linear relationship at the RFP concentration range of 5.0 to 300 nM and the limit of detection was 1.25 nM. The respond time of the MIP@ZAIS QDs was 5 min, and the imprinting factor was 6.3. It also showed good recoveries ranging from 98 to 101%, for analysis of human plasma samples. The method is simple and effective for the detection of RFP and offers a practical application for the rapid analysis of human plasma samples.
Assuntos
Polímeros Molecularmente Impressos , Pontos Quânticos , Rifampina , Sulfetos , Compostos de Zinco , Pontos Quânticos/química , Compostos de Zinco/química , Sulfetos/química , Rifampina/sangue , Rifampina/análise , Rifampina/química , Polímeros Molecularmente Impressos/química , Humanos , Corantes Fluorescentes/química , Impressão Molecular , Espectrometria de Fluorescência , Índio/química , Compostos de Prata/química , Limite de Detecção , Polímeros/químicaRESUMO
In the present study, sisal-Fe/Zn LDH bio-nanocomposite for efficiently removing rifampin was synthesized using a simple co-precipitation method. SEM, XRD, and FTIR analyses were applied to characterize the prepared composite. In the following, different factors that are affecting the adsorption of rifampin, including contact time, initial rifampin concentration, adsorbent dosage, and temperature were evaluated. Also, the kinetic, isotherm, and thermodynamic studies were investigated. The results indicated that Freundlich (R2 = 0.9976) was a suitable model for describing the adsorption equilibrium and adsorption kinetic showed that the data are in maximum agreement with the pseudo-second-order kinetic model (R2 = 0.9931). According to the Langmuir isotherm model, the maximum adsorption capacity of rifampin was found to be 40.00 mg/g. The main mechanisms for rifampin elimination were introduced as electrostatic attraction and physical adsorption. Moreover, the spontaneity and nature of the reaction were analyzed by elucidating thermodynamic factors that indicated the adsorption process was exothermic and spontaneous. Also, the batch process design indicated that for treating 10 L wastewater containing 100 mg/L rifampin with a removal efficiency of 96%, the needed amount of sisal-Fe/Zn LDH is 51.6 g. This study revealed that the sisal-Fe/Zn LDH bio-nanocomposites as a low-cost adsorbent have promising adsorption potential.
In this study, an innovative bio-nanocomposite (sisalFe/Zn layered double hydroxide) has been synthesized using a co-precipitation method for the first time and was used for the removal of pharmaceutical pollutants. SisalFe/Zn LDH exhibited an excellent adsorption capacity of 40.00 mg/g to remove rifampin from the aqueous solution. The main mechanisms for rifampin elimination were introduced as electrostatic attraction and physical adsorption. Also, the batch process design showed that for treating 10 L wastewater containing 100 mg/L rifampin with a removal rate of 96%, the amount of sisalLDH bio-nanocomposite required is about 51.6 g. Therefore, sisalFe/Zn layered double hydroxide as an eco-friendly biosorbent can be considered for future water treatment.
Assuntos
Nanocompostos , Poluentes Químicos da Água , Rifampina/análise , Poluentes Químicos da Água/análise , Concentração de Íons de Hidrogênio , Biodegradação Ambiental , Hidróxidos/análise , Água/análise , Termodinâmica , Cinética , Adsorção , ZincoRESUMO
Antibiotic overuse poses a serious food safety problem. Therefore, it is of great importance to develop efficient assays that respond to antibiotics to establish early-warning mechanisms. Here, we prepared a three-dimensional (3D) porous reduced graphene oxide (pRGO) modified electrode, which was characterized by scanning electron microscopy and transmission electron microscopy. As a result of the introduction of the 3D pRGO film, the electrocatalytic activity was considerably improved, which could efficiently trigger the redox reaction of rifampicin (RIF). By employing differential pulse voltammetry, the reduction peak current of RIF showed a good linear relationship with the logarithm of the RIF concentration in the range 1.0 × 10-9 to 1.0 × 10-7 mol L-1. The linear equation was ip (-10-6 A) = 3.11 + 0.28 log cRIF (R2 = 0.9908) with a detection limit of 2.7 × 10-10 mol L-1 (S/N = 3). Additionally, the final electrode displayed long stability, good reproducibility and high selectivity, and could detect trace RIF in milk with satisfactory results. This study reveals the great potential in utilizing 3D pRGO to develop efficient electrochemical sensors for safeguarding food safety.
Assuntos
Técnicas Eletroquímicas , Rifampina , Animais , Técnicas Eletroquímicas/métodos , Eletrodos , Grafite , Leite/química , Porosidade , Reprodutibilidade dos Testes , Rifampina/análiseRESUMO
Optimised pre-clinical models are required for TB drug development to better predict the pharmacokinetics of anti-tuberculosis (anti-TB) drugs to shorten the time taken for novel drugs and combinations to be approved for clinical trial. Microdialysis can be used to measure unbound drug concentrations in awake freely moving animals in order to describe the pharmacokinetics of drugs in the organs as a continuous sampling technique. The aim of this work was to develop and optimise the microdialysis methodology in guinea pigs to better understand the pharmacokinetics of rifampicin in the lung. In vitro experiments were performed before progressing into in vivo studies because the recovery (concentration of the drug in the tissue fluid related to that in the collected dialysate) of rifampicin was dependent on a variety of experimental conditions. Mass spectrometry of the dialysate was used to determine the impact of flow rate, perfusion fluid and the molecular weight cut-off and membrane length of probes on the recovery of rifampicin at physiologically relevant concentrations. Following determination of probe efficiency and identification of a correlation between rifampicin concentrations in the lung and skeletal muscle, experiments were conducted to measure rifampicin in the sacrospinalis of guinea pigs using microdialysis. Lung concentrations of rifampicin were estimated from the rifampicin concentrations measured in the sacrospinalis. These studies suggest the potential usefulness of the microdialysis methodology to determine drug concentrations of selected anti-TB drugs to support new TB drug development.
Assuntos
Antituberculosos/análise , Pulmão/química , Microdiálise/métodos , Rifampina/análise , Animais , Desenvolvimento de Medicamentos , Feminino , CobaiasRESUMO
Recent efforts in biological engineering have made detection of nucleic acids in samples more rapid, inexpensive and sensitive using CRISPR-based approaches. We expand one of these Cas13a-based methods to detect small molecules in a one-batch assay. Using SHERLOCK-based profiling of in vitrotranscription (SPRINT), in vitro transcribed RNA sequence-specifically triggers the RNase activity of Cas13a. This event activates its non-specific RNase activity, which enables cleavage of an RNA oligonucleotide labeled with a quencher/fluorophore pair and thereby de-quenches the fluorophore. This fluorogenic output can be measured to assess transcriptional output. The use of riboswitches or proteins to regulate transcription via specific effector molecules is leveraged as a coupled assay that transforms effector concentration into fluorescence intensity. In this way, we quantified eight different compounds, including cofactors, nucleotides, metabolites of amino acids, tetracycline and monatomic ions in samples. In this manner, hundreds of reactions can be easily quantified in a few hours. This increased throughput also enables detailed characterization of transcriptional regulators, synthetic compounds that inhibit transcription, or other coupled enzymatic reactions. These SPRINT reactions are easily adaptable to portable formats and could therefore be used for the detection of analytes in the field or at point-of-care situations.
Assuntos
Proteínas de Bactérias/metabolismo , Técnicas Biossensoriais/métodos , Proteínas Associadas a CRISPR/metabolismo , Endodesoxirribonucleases/metabolismo , Ensaios Enzimáticos/métodos , Inibidores da Síntese de Ácido Nucleico/análise , Proteínas de Bactérias/genética , Proteínas Associadas a CRISPR/genética , Sistemas CRISPR-Cas , Endodesoxirribonucleases/genética , Corantes Fluorescentes/química , Leptotrichia , Ligantes , Inibidores da Síntese de Ácido Nucleico/farmacologia , Riboswitch , Rifampina/análise , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacosRESUMO
Rifampicin is a semi-synthetic broad-spectrum antibiotic obtained from rifamycin B. It is one of the most effective first-line antituberculosis drugs and is widely used in clinical practice. In the present study, we describe a rapid and sensitive method for the determination of rifampin in aquatic products by stable isotope-dilution high liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Samples were extracted with the acetonitrile, degreased by hexane, and then concentrated by nitrogen blowing. After separation using a C18 column with a mixture of acetonitrile and water as mobile phase, it was determined by HPLC-MS/MS using the stable isotope-dilution calibration method. The performance of our method was validated. The limit of detection was 0.25 µg kg-1 and the limit of quantification was 0.5 µg kg-1 . At the three spiked levels of 0.5, 1.0 and 5.0 µg kg-1 , the average recoveries of rifampicin in different aquatic products were between 75.28 and 107.6%, and the relative standard deviation ranged from 0.81 to 13.23%. This method was successfully applied for the determination of rifampin in different kinds of aquatic products and rifampicin residue was found in aquatic products obtained from markets in Beijing, China.
Assuntos
Antibacterianos/análise , Cromatografia Líquida de Alta Pressão/métodos , Resíduos de Drogas/análise , Rifampina/análise , Alimentos Marinhos/análise , Espectrometria de Massas em Tandem/métodos , Animais , China , Peixes , Contaminação de Alimentos/análise , Isótopos/análise , Palaemonidae/químicaRESUMO
Rifampicin is a common antibiotic used in human and veterinary medicine to treat tuberculosis and other diseases caused by numerous pathogenic bacteria. However, the excessive or improper use of rifampicin usually leads to a series of problems, including bacterial resistance, excessive drug-resistance and water pollution. Thus, it is of great importance to develop selective and sensitive assays for monitoring rifampicin in biological systems. In this study, we designed a fluorescence "turn-off" strategy for the trace detection of rifampicin based on a glutathione-stabilized copper nanoclusters (GSH-Cu NC) sensor. In an aqueous solution, the fluorescence of the GSH-Cu NCs at 632 nm can be quenched effectively and selectively by rifampicin due to the inner-filter effect (IFE) of fluorescence mechanism. Distinctively, this GSH-Cu NC sensor exhibited excellent fluorescence sensing capability for the trace detection of rifampicin with a very low limit of detection (LOD) of 16 pM in a wide linear range from 50 to 10 000 pM. It is not only more sensitive than the other methods previously reported for the detection of rifampicin, but also has an outstanding selectivity and strong anti-interference in complex samples. Furthermore, the as-developed GSH-Cu NCs were also successfully applied to determine rifampicin in different real samples with quantitative spike recoveries ranging from 97% to 105%.
Assuntos
Cobre/química , Glutationa/química , Limite de Detecção , Nanoestruturas/química , Rifampina/análise , Espectrometria de Fluorescência/instrumentação , Humanos , Soluções Oftálmicas/química , Rifampina/sangue , Rifampina/químicaRESUMO
Reverse phase high pressure liquid chromatography (RP-HPLC) is widely employed in drug discovery for lipophilicity measurements. Hydrophilic interaction liquid chromatography (HILIC) may represent a good alternative to RP-HPLC in the determination of the lipophilicity of hydrophilic compounds like zwitterions. In this paper three different HILIC stationary phases (ZIC®-HILIC, ZIC®-pHILIC and ZIC®-cHILIC) and two different mobile phases (80%ACN/20%buffer and 90%ACN/10%buffer) were combined to set-up six chromatographic systems. A computational tool named Block Relevance (BR) analysis was firstly used to deconvolute the balance of intermolecular forces governing retention in the six systems. Then the lipophilicity profiles (log k vs pH) of ten model ampholytes were determined. Results support that the lipophilicity of zwitterions at any pH can be successfully determined with a ZIC®-cHILIC stationary phase and an 80%ACN/20%buffer mobile phase. To extend the dataset and confirm results, a second series of zwitterionic drugs was also analyzed.
Assuntos
Cromatografia de Fase Reversa/métodos , Interações Hidrofóbicas e Hidrofílicas , Rifampina/análise , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Concentração de Íons de Hidrogênio , Rifampina/químicaRESUMO
Thanks to operational simplicity, speediness, possibility of miniaturization and real-time nature, electrochemical sensing is a supreme alternative for non-electrochemical methodologies in drug quantification. This review, highlights different nanotech-based sensory designs for electroanalysis of isoniazid and rifampicin, the most important medicines for patients with tuberculosis. We first, concisely mention analyses with bare electrodes, associated impediments and inspected possible strategies and then critically review the last two decades works with focus on different nano-scaled electrode modifiers. We organized and described the materials engaged in several categories: Surfactants modifiers, polymeric modifiers, metallic nanomaterials, carbon based nano-modifiers (reduced graphene oxide, multi-walled carbon nanotubes, ordered mesoporous carbon) and a large class of multifarious nano composites-based sensors and biosensors. The main drawbacks and superiorities associated with each array as well as the current trend in the areas is attempted to discuss. Summary of 79 employed electrochemical approaches for analysis of isoniazid and rifampicin has also been presented.
Assuntos
Antituberculosos/análise , Técnicas Eletroquímicas/instrumentação , Isoniazida/análise , Nanoestruturas/química , Rifampina/análise , Técnicas Biossensoriais/instrumentação , Eletrodos , Desenho de Equipamento , Grafite/química , Humanos , Nanotecnologia/métodos , Polímeros/químicaRESUMO
Herein, novel honeycomb like zirconium dioxide with chitosan (ZrO2@chitosan) nanocomposite have been designed through a facile ultrasound-assisted method and followed by a simple sonication process (bath-type ultrasound washer; Honda Electronics-W-118T; 100â¯W/cm2 and 300â¯kHz frequency). After then, as-synthesized ZrO2@chitosan was characterized by FESEM, XRD and EIS. The ZrO2@chitosan nanocomposite modified glassy carbon electrode shows excellent electrochemical sensing performance towards anti-tuberculosis drug (rifampicin). Furthermore, the ZrO2@chitosan modified and fabricated electrochemical sensor showed a wide linear range between 0.015⯵M and 547.4⯵M and nanomolar detection limit (7.5â¯nM). Moreover, the ZrO2@chitosan modified electrode showed selectivity towards the detection of anti-tuberculosis drug (rifampicin). The ZrO2@chitosan nanocomposite film modified non-enzymatic sensor has high stable and good reproducible towards the detection of rifampicin. In addition, the as-synthesized ZrO2@chitosan nanocomposite modified electrode has been applied to the determination of rifampicin in biological samples such as human serum and urine samples.
Assuntos
Antituberculosos/análise , Quitosana/química , Eletroquímica/instrumentação , Limite de Detecção , Nanocompostos/química , Ondas Ultrassônicas , Zircônio/química , Antituberculosos/química , Carbono/química , Técnicas de Química Sintética , Eletrodos , Nanotecnologia , Oxirredução , Reprodutibilidade dos Testes , Rifampina/análise , Rifampina/químicaRESUMO
Antibiotics in water and soil are persistent, bioaccumulative and toxic to aquatic organisms and human health. To address it, as one of the new technologies, green synthesized magnetic Fe3O4 nanoparticles by Excoecaria cochinchinensis extract used to remove rifampicin (RIF) was investigated in this study. Results showed the adsorption efficiency of RIF reached 98.4% and the maximum adsorption capacity is 84.8â¯mg/g when 20â¯mL of RIF at a concentration of 20â¯M was adsorbed by 10â¯mg Fe3O4 at a temperature of 303â¯K. The morphology of the green Fe3O4 characterized by SEM demonstrated the dimensions ranging from 20 to 30â¯nm. The N2 adsorption/desorption isotherms revealed that the surface area of Fe3O4 was 111.8â¯m2/g. In addition, adsorption studies indicated that the kinetics fitted the pseudo second-order and isothermal adsorption conformed to the Langmuir isotherm. Furthermore, due to their magnetic properties, the Fe3O4 nanoparticles were easily separated and reused and the mechanism for removing RIF occurred through adsorption rather than chemical redox reaction. Finally, the reusability of Fe3O4 for adsorption of RIF showed that the removal efficiency decreased to 61.5% after five cycles.
Assuntos
Química Verde/métodos , Rifampina/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Adsorção , Antibacterianos , Compostos Férricos/química , Cinética , Magnetismo , Nanoestruturas/químicaRESUMO
A new carbon paste electrode for rifampicin (RIF) drug was prepared and fully characterized in terms of composition, usable pH range and temperature. The sensor is based on 2-hydroxypropyl ß-cyclodextrin as a good ionophore in the carbon paste matrix. The modified electrode showed a Nernstian slope of 59.2â¯mV/decade over the concentration range of 3.2â¯×â¯10-8 to 2.2â¯×â¯10-4â¯M with a limit of detection 2.3â¯×â¯10-8â¯M. The electrode has a short and stable response time of 4â¯s. The sensor manifested advantages of simple design, low cost, wide concentration range, excellent selectivity to rifampicin, applicable as an indicator electrode and renewability. The sensor was successfully used for determination of rifampicin in tablet and blood serum samples. Temperature dependence of the sensor potential response was examined in the temperature range of 15-55⯰C. The sensor showed a very low thermal coefficient within the studied temperature range.
Assuntos
Técnicas Biossensoriais , Carbono/química , Preparações Farmacêuticas/química , Rifampina/análise , Calibragem , Técnicas Eletroquímicas , Eletrodos , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Padrões de Referência , Rifampina/sangue , Rifampina/química , Soluções , TemperaturaRESUMO
A validated sub minute capillary zone electrophoresis method with direct ultraviolet absorption detection for simultaneous determination of isoniazid and rifampicin in fixed-dose combination tablets was developed. Background electrolyte was defined based on the analytes effective mobility curve and it was composed by 20 mmol/L of sodium carbonate/sodium bicarbonate at pH 10.2. A careful validation procedure considering the main figures of merit was performed. Regression models were satisfactory for isoniazid and rifampicin, showing no lack of fit within 95% significance interval. Interday and intraday precision were evaluated in standard and sample and slight relative standard deviations were achieved for concentration, area, and migration time. Recovery values for accuracy in two levels were 99.97 and 90.08% for isoniazid and 95.45 and 95.12% for rifampicin. The limits of detection for isoniazid and rifampicin were 0.22 and 0.34 mg/L, respectively, and the limits of quantification were 0.74 and 1.13 mg/L, respectively. Method selectivity was verified by injecting diluent, background electrolyte, a standard mixture, and a sample, confirming no interferent peaks. The method proved to be simple, environmentally friendly, sensitive, and was successfully applied for simultaneous quantification of isoniazid and rifampicin in fixed-dose combination tablets.
Assuntos
Isoniazida/análise , Rifampina/análise , Bicarbonato de Sódio/química , Combinação de Medicamentos , Eletroforese Capilar , Espectrofotometria Ultravioleta , Comprimidos/análiseRESUMO
Rifampicin (RIF) and clindamycin phosphate (CDM) are the main drugs currently used in combination to treat severe infectious diseases in hair follicles. This work describes a simple, rapid and sensitive method for simultaneous analysis of RIF and CDM in the different skin layers using high performance liquid chromatography (HPLC). The efficient chromatographic separation of CDM and RIF was succeeded using a C18 column (150â¯mmâ¯xâ¯4.6â¯mm, 5⯵m) with gradient elution using a mobile phase composed of 0.01â¯M phosphoric acid and methanol at a flow rate of 1â¯mL min-1. Determinations were performed using UV-vis detector at 200â¯nm and 238â¯nm for CDM and RIF, respectively. The method was precise, accurate and linear (r2 > 0.999) with regression curve in the concentration range from 0.5 to 20.0⯵gâ¯mL-1 and recovery rates from the skin layers higher than 85%. The retention times for CDM and RIF were approximately 7.4 and 12.2â¯min, respectively. The presence of skin components did not interfere with the analysis. The validated method was therefore appropriate for quantification of both CDM and RIF and thus may be feasible to be used in skin permeation studies.
Assuntos
Técnicas de Química Analítica/normas , Clindamicina/análogos & derivados , Rifampina/análise , Rifampina/metabolismo , Absorção Cutânea/fisiologia , Animais , Antibacterianos/análise , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Antibióticos Antituberculose/análise , Antibióticos Antituberculose/metabolismo , Antibióticos Antituberculose/farmacologia , Técnicas de Química Analítica/métodos , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Clindamicina/análise , Clindamicina/metabolismo , Clindamicina/farmacologia , Técnicas de Cultura de Órgãos , Reprodutibilidade dos Testes , Rifampina/farmacologia , Absorção Cutânea/efeitos dos fármacos , SuínosRESUMO
BACKGROUND: High performance liquid chromatography is an integral analytical tool in assessing drug product stability. HPLC methods should be able to separate, detect, and quantify the various drug-related degradants that can form on storage or manufacturing, plus detect any drug-related impurities that may be introduced during synthesis. OBJECTIVE: A simple, economic, selective, precise, and stability-indicating HPLC method has been developed and validated for analysis of Rifampicin (RIFA) and Piperine (PIPE) in bulk drug and in the formulation. METHOD: Reversed-phase chromatography was performed on a C18 column with Buffer (Potassium Dihydrogen Orthophosphate) pH 6.5 and Acetonitrile, 30:70), (%, v/v), as mobile phase at a flow rate of 1 mL min-1. RESULT: The detection was performed at 341 nm and sharp peaks were obtained for RIFA and PIPE at retention time of 3.3 ± 0.01 min and 5.9 ± 0.01 min, respectively. The detection limits were found to be 2.385 ng/ml and 0.107 ng/ml and quantification limits were found to be 7.228ng/ml and 0.325ng/ml for RIFA and PIPE, respectively. The method was validated for accuracy, precision, reproducibility, specificity, robustness, and detection and quantification limits, in accordance with ICH guidelines. CONCLUSION: Stress study was performed on RIFA and PIPE and it was found that these degraded sufficiently in all applied chemical and physical conditions. Thus, the developed RP-HPLC method was found to be suitable for the determination of both the drugs in bulk as well as stability samples of capsule containing various excipients.
Assuntos
Alcaloides/análise , Benzodioxóis/análise , Piperidinas/análise , Alcamidas Poli-Insaturadas/análise , Rifampina/análise , Alcaloides/química , Benzodioxóis/química , Cápsulas , Cromatografia Líquida de Alta Pressão , Cromatografia de Fase Reversa , Estabilidade de Medicamentos , Hidrólise , Limite de Detecção , Piperidinas/química , Alcamidas Poli-Insaturadas/química , Rifampina/químicaRESUMO
Tuberculosis is the second most deadly infectious disease, surpassed only by HIV/AIDS, and has resulted in over 1 billion deaths in the last 200 years. The World Health Organization estimates that in 2014, 9.6 million people were infected by this disease and 1.5 million had died. First-choice treatment consists of fixed-dose combination tablets containing rifampicin, isoniazid, pyrazinamide, and ethambutol hydrochloride (4-FDC). There are pharmacopeial protocols available to test 4-FDC, but they are prolonged, two-step methods. One single-step method in the literature performs the simultaneous determination by HPLC, but requires a long acquisition time. In this context, an ultra-HPLC (UHPLC) method was developed based on the HPLC method with the objective of reducing analysis time. A C18 column (1.9 µm particle size) was used with UV-diode-array detection at 238 and 282 nm. The method was found to be selective, linear, exact, precise, and robust. Samples from two batches were analyzed and the results compared with those obtained by the HPLC method, with no statistically significant differences observed (P > 0.05). This UHPLC method reduced the analysis time from 17 to 4 min, with a more than 90% reduction in sample and reagent consumption and a financial economy of almost 50-fold.
Assuntos
Antituberculosos/análise , Cromatografia Líquida de Alta Pressão , Etambutol/análise , Isoniazida/análise , Pirazinamida/análise , Rifampina/análiseRESUMO
One of the main obstacles to the successful treatment of tuberculosis is the poor and variable oral bioavailability of rifampicin (RIF), which is mainly due to its low hydrophilicity and dissolution rate. The aim of this work was to obtain a hydrophilic new material that allows a very fast dissolution rate of RIF and therefore is potentially useful in the development of oral solid dosage forms. The acid form of carboxymethylcellulose (CMC) was co-processed with RIF by solvent impregnation to obtain CMC-RIF powder, which was characterized by polarized optical microscopy, powder x-ray diffraction, DSC-TGA, hot stage microscopy, 13C and 15N solid-state NMR and FT-IR spectroscopy. In addition, the CMC-RIF matrices were subjected to water uptake and dissolution studies to assess hydrophilicity and release kinetics. CMC-RIF is a crystalline solid dispersion. Solid-state characterization indicated that no ionic interaction occurred between the components, but RIF crystallized as a zwitterion over the surface of CMC, which drastically increased the hydrophilicity of the solid. The CMC-RIF matrices significantly improved the water uptake of RIF and disintegrated in a very short period immediately releasing RIF. As CMC improves the hydrophilicity and delivery properties of RIF, CMC-RIF is very useful in the design of oral solid dosage forms with very fast dissolution of RIF, either alone or in combination with other antitubercular drugs.
Assuntos
Carboximetilcelulose Sódica/análise , Carboximetilcelulose Sódica/química , Rifampina/análise , Rifampina/química , Varredura Diferencial de Calorimetria/métodos , Espectroscopia de Ressonância Magnética/métodos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Fatores de Tempo , Difração de Raios X/métodosRESUMO
In this study, we describe the synthesis of a new quantum dots (QDs) by embedding glutathione capped CdTe/ZnS QDs into cationic starch biopolymer (CS-GSH-CdTe/ZnS QDs). The fluorescence intensity of prepared QDs was significantly enhanced. When QDs interacted with rifampicin, the fluorescence intensity of the CS-GSH-CdTe/ZnS QDs was highly quenched compared with GSH-CdTe/ZnS QDs. Based on the above, a new fluorescent nanosensor for simple, sensitive and selective detection of rifampicin was developed. The fluorescence quenching was well described by the typical Stern-Volmer equation. After optimization, the linear range of the as-prepared QDs fluorescence intensity versus the concentration of rifampicin was F0/F=0.0422Q+1.109 (R2=0.99). The detection limit was 0.06×10-6mol/L. The proposed method with satisfactory results was used to detect rifampicin in commercial capsules and tablets.