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1.
Rapid Commun Mass Spectrom ; 37(2): e9425, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36329637

RESUMO

RATIONALE: Tuberculosis (TB) remains a challenging global infectious disease, mainly affecting the lungs. First-line anti-TB drugs play a crucial role in slowing down the rapid spread of TB. In addition, the patient might benefit from therapeutic drug monitoring since it has become an accepted clinical tool for optimizing TB treatment. METHODS: A simple and sensitive liquid chromatography/tandem mass spectrometry method was developed to monitor the plasma level of isoniazid, ethambutol and pyrazinamide in plasma samples. A one-step extraction procedure using an Ostro™ plate was applied, and extracts were analyzed by gradient elution followed by detection on a mass spectrometer by multiple reaction monitoring mode. RESULTS: The analytes were separated within 4.2 min and over the concentration range of 0.2-10 µg/ml for isoniazid and ethambutol and 1-65 µg/ml for pyrazinamide. The method was successfully validated according to the European Medicine Agency guideline for the selectivity, linearity and lower limit of detection, precision and accuracy, matrix effect, extraction recovery, carryover, dilution integrity and stability, and applied for quantification of analytes in clinical samples from TB patients. CONCLUSIONS: The presented method allows sensitive and reproducible determination of selected anti-TB drugs with advantages such as low sample volume requirement, short run time of analysis, one-step sample preparation procedure with capabilities for phospholipids removal, and a low quantification limit as well as a high degree of selectivity.


Assuntos
Etambutol , Tuberculose , Humanos , Etambutol/análise , Etambutol/uso terapêutico , Pirazinamida/análise , Pirazinamida/uso terapêutico , Isoniazida/uso terapêutico , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Antituberculosos , Tuberculose/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos
2.
Magn Reson Chem ; 59(7): 746-751, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33742475

RESUMO

Favipiravir is an established antiviral that is currently being assessed as an investigational drug for the treatment of COVID-19. Favipiravir is strikingly similar to two molecules that the World Health Organization (WHO) lists as essential medicines, which also consist of a six-membered aromatic N-heterocycle bearing a carboxamide function: the anti-tuberculosis agent, pyrazinamide, and nicotinamide, also known as vitamin B3 . We demonstrate the utility of 1 H nuclear magnetic resonance (NMR) profiling, an emerging pharmacopoeial tool, for the highly specific identification, selective differentiation of congeners, and subsequent detection of drug falsification or adulteration of these medicines. The straightforward comparison of basic 1-D 1 H NMR spectra, obtained with benchtop or advanced NMR instruments alike, offers a rapid identity assay and works independently of physical reference materials. This approach accelerates and advances pharmaceutical quality control measures under situations of increased drug demand and altered economy, such as during a pandemic.


Assuntos
Amidas/análise , Antivirais/análise , Contaminação de Medicamentos/prevenção & controle , Niacinamida/análise , Pirazinamida/análise , Pirazinas/análise , Controle de Qualidade , Amidas/química , Antivirais/química , Niacinamida/química , Espectroscopia de Prótons por Ressonância Magnética , Pirazinamida/química , Pirazinas/química , Organização Mundial da Saúde
3.
Talanta ; 205: 120138, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31450409

RESUMO

Herein, we report a novel composite fabricated via embedding rod-like Co based metal-organic framework (Co-MOF-74) crystals into MC matrix for the first time. The introduction of MC astricts the size of Co-MOF-74 crystals, enlarges the pore size and improves the electrical conductivity, which lead to the good electrochemical properties of the composite. The fabricated sensor based on Co-MOF-74@MC exhibits superior electrocatalytic activity toward the reduction of pyrazinamide (PZA) and the oxidation of isonicotinyl hydrazide (INZ). Under optimized conditions, the sensor shows two linear ranges from 0.3 to 46.5 µM and 46.5-166.5 µM with a high sensitivity of 7.2 µA µM-1 cm-2 and a detection limit of 0.21 µM for the determination of PZA. The electroanalytical sensing of INZ also gives two linear ranges of 0.15-1.55 µM and 1.55-592.55 µM with a detection limit of 0.094 µM. The mechanism involved was also discussed, briefly. The sensor is assessed toward the detection of PZA and INZ in human serum and urine samples. Recovery values varied from 97.08 to 103.20% for PZA sensing and 96.67-102.90% for INZ sensing, revealing the promising practicality of sensor for PZA and INZ detection.


Assuntos
Análise Química do Sangue/métodos , Carbono/química , Cobalto/química , Vidro/química , Isoniazida/análise , Estruturas Metalorgânicas/química , Pirazinamida/análise , Urinálise/métodos , Análise Química do Sangue/instrumentação , Catálise , Eletroquímica , Eletrodos , Humanos , Isoniazida/sangue , Isoniazida/química , Isoniazida/urina , Limite de Detecção , Oxirredução , Porosidade , Pirazinamida/sangue , Pirazinamida/química , Pirazinamida/urina , Urinálise/instrumentação
4.
J Pharm Biomed Anal ; 168: 44-54, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30784889

RESUMO

Tuberculosis is one of the top concerns in the world and acutely threatens human health. A new potent candidate regimen containing pyrazinamide (PZA), ethambutol (EMB), protionamide (PTO) and clofazimine (CFZ) was proposed by Parabolic Response Surface/Feedback System Control (FSC/PRS) system and showed excellent outcomes in vitro and vivo studies. Here, a convenient liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneously determination of four compounds in beagle dog plasma. The plasma samples, 50 µL for each, were pretreated by methanol on 96-well format plates and a further dilution step was designed to reduce predictable matrix effect and lessen the burden of subsequent analysis. The chromatographic separation was achieved on an Agilent SB-Aq column (4.6 mm × 150 mm, 5 µm) at 30 °C by a gradient elution within 6 min. The mobile phase was a mixture of 0.2% formic acid-5 mM ammonium acetate aqueous solution (phase A) and 0.2% formic acid methanol (phase B) with a total flow rate of 1 mL/min. The 30% of post-column eluant was injected into mass spectrometer, equipped with electrospray ionization (ESI) source under positive mode and multiple-reaction monitoring (MRM). This quantification method was proved to be satisfied in selectivity, accuracy, precision, linearity (r2 > 0.998), recovery, matrix effect and stability. Under the specialized conditions, the calibration curves ranged from 20 to 5000 ng/mL for PZA, 1 to 500 ng/mL for EMB, 1 to 500 ng/mL for PTO, and 1 to 200 ng/mL for CFZ. The quantitative accuracy was further assessed under different degrees of hemolyses in detail. This method was proved to be robust and efficient, and successfully applied to the pharmacokinetic study of the new regimen in Beagle dogs.


Assuntos
Antituberculosos/análise , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Animais , Antituberculosos/farmacocinética , Calibragem , Clofazimina/análise , Clofazimina/farmacocinética , Cães , Etambutol/análise , Etambutol/farmacocinética , Protionamida/análise , Protionamida/farmacocinética , Pirazinamida/análise , Pirazinamida/farmacocinética , Reprodutibilidade dos Testes
5.
J AOAC Int ; 100(4): 1008-1015, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28720173

RESUMO

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/análise
6.
J Pharm Biomed Anal ; 135: 133-139, 2017 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-28024261

RESUMO

A simple and sensitive reversed phase HPLC method has been developed for the simultaneous quantitation of pretomanid (PA-824), moxifloxacin and pyrazinamide in a combination spray-dried powder formulation for inhalation, without any use of an internal standard. Good resolution of the analytes was achieved on a Luna C18 (2), 150×4.6mm, 5µm, 100Å column using gradient elution with a mobile phase containing methanol and triethylamine phosphate buffer (pH 2.5) at a flow rate of 1.0mL/min in a total run time of 25min. Pyrazinamide, moxifloxacin and pretomanid (PA-824) were detected at wavelengths (retention times) of 269nm (3.80min), 296nm (7.94min) and 330nm (17.46min), respectively. The assay was linear for all analytes in the concentration range 2.5-100µg/mL (correlation coefficients >0.999) with LODs and LLOQs (µg/mL) of pretomanid (PA-824) 0.51 and 1.56, moxifloxacin 0.06 and 0.19 and pyrazinamide 0.35 and 1.06, respectively. Recoveries of the three drugs were 99.6-106.8% with intra- and inter-day precisions (as relative standard deviation) of <7%. The method was successfully applied to an evaluation of content uniformity and freedom from interference by l-leucine of a spray-dried combination powder for inhalation.


Assuntos
Antituberculosos/análise , Química Farmacêutica/métodos , Fluoroquinolonas/análise , Nitroimidazóis/análise , Pirazinamida/análise , Tuberculose Resistente a Múltiplos Medicamentos , Administração por Inalação , Antituberculosos/química , Cromatografia Líquida de Alta Pressão/métodos , Composição de Medicamentos , Fluoroquinolonas/química , Moxifloxacina , Nitroimidazóis/química , Pirazinamida/química
7.
APMIS ; 124(11): 1004-1015, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27546025

RESUMO

A remediable cause of poor treatment response in drug-susceptible tuberculosis (TB) patients may be low plasma levels of one or more of the first-line anti-TB drugs. The aim of this work was to develop an accurate and precise LC-MS/MS method for simultaneous quantification of all four first-line anti-TB drugs in plasma suitable for therapeutic drug monitoring (TDM). To adjust for degradation and losses during sample preparation, isotopically labeled compounds were used as internal standards. Plasma samples spiked with internal standards were extracted using protein precipitation with methanol and acetonitrile. Simultaneous separation of all four drugs was accomplished with a Chromolith Reversed-Phase column and mobile phases consisting of water, methanol, ammonium acetate and formic acid with subsequent mass spectrometric quantification. The linear range of the calibration curve for isoniazid was 0.5-10 mg/L, for rifampicin 0.75-30 mg/L, for ethambutol 0.25-10 mg/L and for pyrazinamide 4-80 mg/L. The lower limit of quantification was 0.5 mg/L, 0.75 mg/L, 0.25 mg/L and 4.0 mg/L, respectively. Precision estimated by the coefficient of variation was <15% for all four drugs. The LC-MS/MS method can readily be used for simultaneous quantification of first-line anti-TB drugs in plasma and is well suited for TDM.


Assuntos
Antituberculosos/análise , Cromatografia Líquida/métodos , Etambutol/análise , Isoniazida/análise , Pirazinamida/análise , Rifampina/análise , Espectrometria de Massas em Tandem/métodos , Monitoramento de Medicamentos/métodos , Humanos , Plasma/química
8.
J AOAC Int ; 98(5): 1234-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26525241

RESUMO

Tuberculosis treatment consists of a fixed dose combination of rifampicin (RIF), isoniazid (INH), pyrazinamide (PYZ), and ethambutol hydrochloride (EMB). The combined treatment using various drugs is necessary for patient curing, without recrudescence, and for prevention of drug-resistant mutants, which may occur during treatment. An HPLC-diode array detector (DAD) method for the simultaneous determination of RIF, INH, PYZ, and EMB in fixed dose combination tablets was developed and validated. Chromatographic experiments were performed on an Agilent 1200 HPLC system, and the separation was carried out on a Purospher STAR RP18e (250×4.6 mm id, 5 µm, Merck) analytical column. Gradient elution was carried out with a mobile phase of 20 mM monobasic sodium phosphate buffer with 0.2% triethylamine (pH 7.0) and acetonitrile at a flow rate of 1.5 mL/min. The total run time was 12 min, and the re-equilibration time was 5 min. EMB detection was performed at 210 nm, and RIF, INH, and PYZ were detected at 238 nm, using a DAD. The method proved to be specific, linear (r2>0.99), precise (RSD<2%), accurate, and robust and may be applied to the QC analysis of pharmaceutical formulations.


Assuntos
Antituberculosos/análise , Cromatografia Líquida de Alta Pressão/métodos , Etambutol/análise , Isoniazida/análise , Pirazinamida/análise , Rifampina/análise , Acetonitrilas/química , Combinação de Medicamentos , Etilaminas/química , Análise de Injeção de Fluxo , Humanos , Sensibilidade e Especificidade , Comprimidos
9.
Chemosphere ; 121: 68-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25434276

RESUMO

In this study, a multisyringe chromatography system (MSC) using a C18 monolithic column was proposed for the on-line monitoring of the photocatalytic degradation of isoniazid (INH, 10 mg L(-1)) and pyrazinamide (PYRA, 5mgL(-1)) mixtures in aqueous solution using a small sample volume (200 µL) with an on-line filtration device in a fully automated approach. During the photocatalytic oxidation using TiO2 or ZnO semiconductor materials, total organic carbon (TOC) and the formed intermediates were analyzed off-line using ion chromatography, ion exclusion HPLC, and ESI-MS/MS. The results showed that TiO2 exhibits a better photocatalytic activity than ZnO under UV irradiation (365 nm) for the degradation of INH and PYRA mixtures, generating 97% and 92% degradation, respectively. The optimal oxidation conditions were identified as pH 7 and 1.0 g L(-1) of TiO2 as catalyst. The mineralization of the initial organic compounds was confirmed by the regular decrease in TOC, which indicated 63% mineralization, and the quantitative release of nitrate and nitrite ions, which represent 33% of the nitrogen in these compounds. The major intermediates of INH degradation included isonicotinamide, isonicotinic acid, and pyridine, while the ESI-MS/MS analysis of PYRA aqueous solution after photocatalytic treatment showed the formation of pyrazin-2-ylmethanol, pyrazin-2-ol, and pyrazine. Three low-molecular weight compounds, acetamide, acetic acid and formic acid, were detected during INH and PYRA decomposition. PYRA was more resistant to photocatalytic degradation due to the presence of the pyrazine ring, which provides greater stability against OH attack.


Assuntos
Antituberculosos/isolamento & purificação , Monitoramento Ambiental/métodos , Isoniazida/isolamento & purificação , Pirazinamida/isolamento & purificação , Poluentes Químicos da Água/isolamento & purificação , Purificação da Água/métodos , Antituberculosos/análise , Antituberculosos/efeitos da radiação , Catálise , Cromatografia Líquida de Alta Pressão , Monitoramento Ambiental/instrumentação , Desenho de Equipamento , Isoniazida/análise , Isoniazida/efeitos da radiação , Oxirredução , Processos Fotoquímicos , Pirazinamida/análise , Pirazinamida/efeitos da radiação , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Titânio/química , Raios Ultravioleta , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/efeitos da radiação , Purificação da Água/instrumentação , Óxido de Zinco/química
10.
PLoS One ; 9(7): e102047, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25004128

RESUMO

SETTING: In most developing countries, paediatric tuberculosis is treated with split tablets leading to potential inaccuracy in the dose delivery and drug exposure. There is no data on the quality of first-line drugs content in split fixed-dose combination tablets. OBJECTIVE: To determine Isoniazid, Pyrazinamide and Rifampicin content uniformity in split FDC tablets used in the treatment of childhood tuberculosis. DESIGN: Drug contents of 15 whole tablets, 30 half tablets and 36 third tablets were analysed by high performance liquid chromatography. The content uniformity was assessed by comparing drug content measured in split portions with their expected amounts and the quality of split portions was assessed applying qualitative specifications for whole tablets. RESULTS: All whole tablets measurements fell into the USP proxy for the three drugs. But a significant number of half and third portions was found outside the tolerated variation range and the split formulation failed the requirements for content uniformity. To correct for the inaccuracy of splitting the tablets into equal portions, a weight-adjustment strategy was used but this did not improve the findings. CONCLUSION: In split tablets the content of the three drugs is non-uniform and exceeded the USP recommendations. There is an absolute need to make child-friendly formulations available for the treatment of childhood tuberculosis.


Assuntos
Isoniazida/análise , Pirazinamida/análise , Rifampina/análise , Química Farmacêutica/normas , Combinação de Medicamentos , Humanos , Isoniazida/uso terapêutico , Pirazinamida/uso terapêutico , Controle de Qualidade , Rifampina/uso terapêutico , Comprimidos , Tuberculose Pulmonar/tratamento farmacológico
11.
J Pharm Biomed Anal ; 97: 1-8, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24798753

RESUMO

A simple, sensitive and rapid LC-MS/MS method has been developed and validated for simultaneous determination of PA-824, moxifloxacin, and pyrazinamide in rat plasma using metronidazole as internal standard. Sample preparation involved a simple one-step protein precipitation with methanol, followed by centrifugation and evaporation of the organic solvent. The residue was redissolved in mobile phase and analyzed by LC-MS/MS. An Inertsil(®) ODS3 C18 column (150mm×4.6mm, 5µm), a mobile phase composed of methanol-0.03% TEA (triethylamine) in water (85:15, v/v), and a flow rate of 0.5mL/min were employed, and the total run time was 6.0min. The mass spectrometer was run in positive ion ESI-APCI combined mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The LLOQ was 1.0µg/mL for pyrazinamide and 0.1µg/mL for PA-824 and moxifloxacin. The recoveries obtained for PA-824, moxifloxacin and pyrazinamide were ≥85%. Intra-day and inter-day coefficients of variation were less than 10%. The method had been successfully applied to a pharmacokinetic study of fixed dose administration of PA-824, moxifloxacin, pyrazinamide and their combination in SD rat. Significant differences of Tmax, Cmax, AUC(0-t) and CLz/F were observed between the single and combined groups after equal dose of PA-824 and moxifloxacin administration, which revealed the possibility of drug-drug interaction (DDI) between the PaMZ combination.


Assuntos
Fluoroquinolonas/análise , Fluoroquinolonas/farmacocinética , Nitroimidazóis/análise , Nitroimidazóis/farmacocinética , Plasma/química , Pirazinamida/análise , Pirazinamida/farmacocinética , Animais , Cromatografia Líquida/métodos , Interações Medicamentosas , Limite de Detecção , Metronidazol/análise , Moxifloxacina , Ratos , Espectrometria de Massas em Tandem/métodos
12.
J Pharm Sci ; 103(3): 937-44, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24425102

RESUMO

The aim of this work is to monitor the changes in microstructure in nonionic Brij 96 microemulsions and to locate the solubilization loci of antituberculosis drugs (of variable solubility using photophysical and thermoanalytical properties. Using properties such as spectral shift, Stroke's shift, and anisotropy for two dyes, that is, Nile red (NR) and tris(2,2'-bipyridine)ruthenium(II) dichloride (RC), the structure of microemulsions has been investigated. With the help of spectral and deconvoluted analysis, it has been seen that rifampicin (RIF) shows a strong interaction with NR and isoniazid (INH) and pyrazinamide (PZA) with RC. It has been concluded that RIF molecules are mainly present at the interface toward oil side and INH toward hydrophilic side, whereas PZA remains in free water. The findings have been correlated with aqueous solubility drugs and partition coefficients. Differential scanning calorimetry elucidates the state of water in microheterogeneous environment and variation of different states, that is, free, bound, interphasal, and nonfreezable water with dilution. In addition, it confirmed the stability and location of the drugs in the prepared Brij 96 microemulsion formulations. A good agreement between both the studies has been achieved. These findings will help in elucidating the drug delivery properties of anti-TB drugs-loaded microemulsion formulations in future.


Assuntos
Antituberculosos/química , Portadores de Fármacos/química , Isoniazida/química , Modelos Químicos , Óleos de Plantas/química , Polietilenoglicóis/química , Pirazinamida/química , Rifampina/química , 2,2'-Dipiridil/análogos & derivados , 2,2'-Dipiridil/química , Antituberculosos/análise , Varredura Diferencial de Calorimetria , Complexos de Coordenação , Portadores de Fármacos/análise , Composição de Medicamentos , Estabilidade de Medicamentos , Emulsões , Polarização de Fluorescência , Corantes Fluorescentes/química , Interações Hidrofóbicas e Hidrofílicas , Isoniazida/análise , Oxazinas/química , Pirazinamida/análise , Rifampina/análise , Solubilidade , Espectrometria de Fluorescência , Água/análise
13.
Trop Med Int Health ; 18(9): 1141-1144, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23937703

RESUMO

OBJECTIVE: To determine the content of certain antituberculosis (TB) drugs supplied at TB treatment centres of the Revised National TB Control Programme (RNTCP) in the state of Tamil Nadu, India. METHODS: Eight districts across the state were selected, and the following drugs were collected from five settings (District TB centre, TB unit, designated microscopy centres, DOT providers) in each district: rifampicin (150 and 450 mg), isoniazid (300 mg), pyrazinamide (500 and 750 mg), ethambutol (400 and 600 mg), ethionamide (250 mg), levofloxacin (500 mg) and cycloserine (250 mg). A maximum of 10 tablets/capsules were collected from each setting. The drugs were coded prior to analysis. All drugs were assayed by validated spectrophotometric methods. The acceptable limits for drug content were taken as 90-110% of the stated content. RESULTS: More than 90% of tablets of rifampicin 450 mg, isoniazid 300 mg, pyrazinamide 500 and 750 mg, ethambutol 400 and 600 mg and ethionamide 250 mg were within acceptable limits. Eighty per cent of rifampicin 150 mg, 21% of cycloserine 250 mg and 87% of levofloxacin 500 mg were within acceptable limits. The mean cycloserine content was below the acceptable limit in all districts, the mean drug content being 200 mg (range: 108-245 mg). CONCLUSION: This systematic study showed that the stated drug content of cycloserine was not reached in all districts. Deterioration of cycloserine could be minimised by storing the drug in refrigerators. The geographical location of the districts had no influence on the drug content.


Assuntos
Antituberculosos/análise , Antituberculosos/normas , Tuberculose/tratamento farmacológico , Antituberculosos/uso terapêutico , Ciclosserina/análise , Ciclosserina/normas , Ciclosserina/uso terapêutico , Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Armazenamento de Medicamentos/normas , Quimioterapia Combinada/normas , Etambutol/análise , Etambutol/normas , Etambutol/uso terapêutico , Etionamida/análise , Etionamida/normas , Etionamida/uso terapêutico , Humanos , Índia , Isoniazida/análise , Isoniazida/normas , Isoniazida/uso terapêutico , Levofloxacino , Ofloxacino/análise , Ofloxacino/normas , Ofloxacino/uso terapêutico , Pirazinamida/análise , Pirazinamida/normas , Pirazinamida/uso terapêutico , Rifampina/análise , Rifampina/normas , Rifampina/uso terapêutico , Espectrofotometria
14.
AAPS PharmSciTech ; 14(4): 1313-20, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23990078

RESUMO

Ethionamide (ETA) and pyrazinamide (PZA) are considered the drugs of choice for the treatment of multidrug-resistant tuberculosis. Current methods available in the literature for simultaneous determination of ETA and PZA have low sensitivity or involve column modifications with lipophilic cations. The aim of this study was to develop a simple and validated reversed-phase ion-pair HPLC method for simultaneous determination of ETA and PZA for the characterization of polymeric-based porous inhalable microparticles in in vitro and spiked human serum samples. Chromatographic separation was achieved on a Phenomenex C18 column (250 mm × 4.6 mm) using a Shimadzu LC 10 series HPLC. The mobile phase consisted of A: 0.01% trifluoroacetic acid in distilled water and B: ACN/MeOH at 1:1 v/v. Gradient elution was run at a flow rate of 1.5 mL/min and a fixed UV wavelength of 280 nm. The validation characteristics included accuracy, precision, linearity, analytical range, and specificity. Calibration curves at seven levels for ETA and PZA were linear in the analytical range of 0.1-3.0 µg/mL with correlation coefficient of r (2) > 0.999. Accuracy for both ETA and PZA ranged from 94 to 106% at all quality control (QC) standards. The method was precise with relative standard deviation less than 2% at all QC levels. Limits of quantitation for ETA and PZA were 50 and 70 ng/mL, respectively. There was no interference from either the polymeric matrix ions or the biological matrix in the analysis of ETA and PZA.


Assuntos
Antituberculosos/análise , Etionamida/análise , Pirazinamida/análise , Algoritmos , Calibragem , Cromatografia Líquida de Alta Pressão , Cromatografia por Troca Iônica , Limite de Detecção , Nanopartículas , Porosidade , Padrões de Referência , Reprodutibilidade dos Testes , Soluções
15.
J Chromatogr A ; 1260: 232-8, 2012 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-22981506

RESUMO

This paper presents the development of a new RP-HPTLC method for the separation of pyrazinamide, isoniazid, rifampicin and ethambutol in a four fixed-dose combination (4 FDC) tablet formulation. It is a single method with two steps in which after plate development pyrazinamide, isoniazid and rifampicin are detected at an UV wavelength of 280 nm. Then ethambutol is derivatized and detected at a VIS wavelength of 450 nm. Methanol, ethanol and propan-1-ol were evaluated modifiers to form alcohol-water mobile phases. Systematic optimization of the composition of each alcohol in the mobile phase was carried out using the window diagramming concept to obtain the best separation. Examination of the Rf distribution of the separated compounds showed that separation of the compounds with the mobile phase containing ethanol at the optimal fraction was almost situated within the optimal Rf-values region of 0.20-0.80. Therefore, ethanol was selected as organic modifier and the optimal mobile phase composition was found to be ethanol, water, glacial acetic acid (>99% acetic acid) and 37% ammonia solution (70/30/5/1, v/v/v/v). The method is new, quick and cheap compared to the actual method in the International Pharmacopoeia for the assay of the 4 FDC tablets, which involves the use of two separate HPLC methods.


Assuntos
Cromatografia de Fase Reversa/métodos , Cromatografia em Camada Fina/métodos , Etambutol/isolamento & purificação , Isoniazida/isolamento & purificação , Pirazinamida/isolamento & purificação , Rifampina/isolamento & purificação , Antituberculosos/análise , Antituberculosos/isolamento & purificação , Etambutol/análise , Etanol/química , Isoniazida/análise , Pirazinamida/análise , Reprodutibilidade dos Testes , Rifampina/análise , Comprimidos/química
16.
J AOAC Int ; 92(3): 830-6, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19610375

RESUMO

Finding counterfeit drugs presents a growing challenge in preventing these products from entering health systems and causing serious consequences for consumers, drug manufacturers, and governments. In this investigation a simple, low-cost, and expeditious chemiluminometric approach, relying on a fully automated multipumping flow system for screening pharmaceutical preparations of the antituberculosis drug pyrazinamide, was implemented. The developed chemiluminescent method was based on the scavenging effect of pyrazinamide on the oxidation of luminol by hydrogen peroxide in alkaline medium. For analytical signal monitoring, a homemade chemiluminescence detector relying on a photomultiplier module was developed. Linear calibration plots for pyrazinamide concentrations between 10 and 70 mg/L were obtained (R = 0.9931) with good precision (RSD < 0.99%; n = 21). The limit of detection was 5.79 mg/L, and the sampling rate was about 150 determinations per hour.


Assuntos
Antituberculosos/análise , Fraude , Medições Luminescentes/métodos , Pirazinamida/análise
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 28(8): 1814-8, 2008 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-18975810

RESUMO

Since 1980s, tuberculosis has become increasingly serious. Rifampicin tablets, isoniazide tablets, pyrazinamide tablets, rifampicin and isoniazide tablets and rifampicin isoniazide and pyrazinamide tablets are currently relatively efficacious antituberculosis drugs. In the present paper, near infrared spectroscopy (NIRS) with partial least squares (PLS) was applied to the simultaneous determination of rifampicin (RMP), isoniazide (INH) and pyrazinamide (PZA) contents in 5 varieties of anti-tuberculosis tablets. As the results showed, all of the models for the determination of RMP, INH and PZA contents applied the original NIR spectra. The most efficacious wavelength range for the determination of RMP contents was 1981-2195 nm, it was 1540-1717 nm and 2086-2197 nm for the determination of INH contents, and it was 1460-1537 nm, 1956-2022 nm and 2268-2393 nm for determination of PZA contents. The root mean square error of the calibration set obtained by cross-validation (RMSECV) of the optimum models for the quantitative analysis of RMP, INH and PZA contents was 0.0494, 0.0257 and 0.0307, respectively. Using these optimum models for the determination of RMP, INH and PZA contents in prediction set, the root mean square error of prediction set (RMSEP) was 0.0182, 0.0166 and 0.0134, respectively. The correlation coefficient (r(p)) between the predicted values and actual values was 0.9864, 0.9989 and 0.9993, respectively. These results demonstrated that this method was precise and reliable, and is significative for in situ measurement and the on-line quality control for anti-tuberculosis tablets production.


Assuntos
Antituberculosos/análise , Rifampina/análise , Espectroscopia de Luz Próxima ao Infravermelho , Algoritmos , Antituberculosos/química , Isoniazida/análise , Modelos Químicos , Análise de Componente Principal , Pirazinamida/análise , Rifampina/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Comprimidos/análise , Comprimidos/química
19.
J Chromatogr Sci ; 45(1): 38-44, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17254382

RESUMO

The aim of this study is to develop and optimize a simple and reliable high-performance liquid chromatography (HPLC) method for the simultaneous determination of rifampicin (RIF), isoniazid (INH), and pyrazinamide (PZA) in a fixed-dose combination. The method is developed and optimized using an artificial neural network (ANN) for data modeling. Retention times under different experimental conditions (solvent, buffer type, and pH) and using four different column types (referred to as the input and testing data) are used to train, validate, and test the ANN model. The developed model is then used to maximize HPLC performance by optimizing separation. The sensitivity of the separation (retention time) to the changes in column type, concentration, and type of solvent and buffer in the mobile phase are investigated. Acetonitrile (ACN) as a solvent and tetrabutylammonium hydroxide (tBAH), used to adjust pH, have the greatest influence on the chromatographic separation of PZA and INH and are used for the final optimization. The best separation and reasonably short retention times are produced on the micro-bondapak C18, 4.6 x 250-mm column, 10 microm/125 A using ACN-tBAH (42.5:57.5, v/v) (0.0002M) as the mobile phase, and optimized at a final pH of 3.10.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Isoniazida/análise , Redes Neurais de Computação , Pirazinamida/análise , Rifampina/análise , Disponibilidade Biológica , Combinação de Medicamentos , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Rifampina/farmacocinética , Sensibilidade e Especificidade
20.
J Mol Model ; 13(4): 505-18, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17260147

RESUMO

Three of the most frequent antitubercular agents employed against Mycobacterium tuberculosis are: Rifampicin, Isoniazid and Pyrazinamide. It has been proven that the use of these antitubercular agents together, shortens the treatment period from 12-18 months to 6 months [1]. In this work we use a new Density Functional Theory chemistry model called CHIH-DFT (Chihuahua-Heterocycles-Density Functional Theory) that reflects the mixture of Hartree Fock exchange and DFT exchange, according to a mixing parameter based on empirical rules suited for heterocyclic systems. This new chemistry model was used to calculate the molecular structure of these antitubercular compounds, as well as their infrared, UV spectra, chemical reactivity and electronic properties. The UV and infrared spectra were obtained by experimental techniques. The calculated molecular structure, UV and IR spectra values from CHIH-DFT were compared with experimentally obtained values and theoretical studies. These results are in good agreement with experimental and theoretical studies. We also predicted using the relative electrophilicity and relative nucleophilicity concepts as defined by Roy et al. [2] the chemical active sites for the three antitubercular compounds as well as their electronegativity, ionization potential, electron affinity, hardness, dipole moment, E(HOMO)-E(LUMO) gap energy, etc.


Assuntos
Antituberculosos/análise , Antituberculosos/química , Isoniazida/análise , Isoniazida/química , Pirazinamida/análise , Pirazinamida/química , Rifampina/análise , Rifampina/química , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta
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