Simultaneous Determination Of Rifampicin Research Articles

Simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol in fixed-dose combination antituberculosis pharmaceutical formulations: a review

According to the World Health Organization, rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are the first-line drugs used to treat tuberculosis – an infectious disease caused by Mycobacterium tuberculosis.

Simultaneous determination of rifampicin, isoniazid, pyrazinamide and ethambutol in 4-FDC tablet by Raman spectroscopy associated to chemometric approach

Tuberculosis is mainly treated by fixed dose combination therapy containing mainly rifampicin, isoniazid, pyrazinamide and ethambutol. The quality control of these drugs in these formulations is very important because of high incidence of resistance to these drugs. Most of the analytical methods developed for the quantification analyze these drugs individually and they are laborious, costly, and time consuming. The present work aims at developing an alternative analytical method addressing these limitations of the traditional methods A Raman spectroscopic method was developed to simultaneously estimate all these four first line antituberculosis drugs. This method has addressed all these limitations of traditional methods as it was very simple, rapid and cost effective. Calibration and validation samples of these drugs were prepared with a wider range and analyzed by both Raman and HPLC. Various figures of merit were determined for the developed method to evaluate the efficacy and quality of the method. Partial Least Squares regression (PLS) approach was used in Raman spectroscopic method to quantify the drugs. Correlation graphs and paired t test were used to compare these two analytical. Based on the results obtained, Raman spectroscopic method was found to be an efficient alternative for the simultaneous estimation of rifampicin, isoniazid, pyrazinamide and ethambutol. These results also indicate that the developed Raman method can be used as a screening technique in the quality control of fixed dose combination products for the therapy of tuberculosis.

Development and validation of high-performance thin-layer chromatographic method for the simultaneous determination of rifampicin, isoniazid, and pyrazinamide in a fixed dosage combination tablet

Despite being a controllable, preventable, and curable disease,tuberculosis (TB) still remains as a major public health problemin many parts of the world [1, 2]. It is the second leading causeof death from infectious diseases (4% of all deaths), and 88 mil-lion new cases of TB occurred throughout the world during thelast decade [3]. Latent TB infection is present in two billion peo-ple, and 7–8 million new cases are added each year [4, 5].Tuberculosis (TB) is a disease that may have first been identi-fied over 15,000 years ago. Even a century after the discovery ofits cause,

Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC–MS/MS

Rifampicin (RIF) and clarithromycin (CLR) are common drugs for the treatment of infections like Mycobacterium tuberculosis and Mycobacterium ulcerans. Treatment for these diseases are long-term and the individual pharmacokinetic variation, drug-drug interactions or non-adherence may introduce sub-therapeutic exposure or toxicity. The application of therapeutic drug monitoring (TDM) can be used to ensure efficacy and avoid toxicity. With the use of dried blood spot (DBS), TDM may be feasible in rural areas. During DBS method development, unexpected interactions or matrix effects may be encountered due to endogenous components in the blood. Another complication compared to plasma analysis is that RIF can form chelate complexes with ferric ions or can bind with hemes, which are potentially present in the extracts of dried blood spots. The investigation focused on the interaction between RIF and the endogenous components of the DBS. The use of ethylenediaminetetraacetic acid (EDTA) and deferoxamine (DFX) as chelator agents to improve recoveries and matrix effects were investigated. A rapid analytical method was developed and validated to quantify RIF and CLR and their active metabolites desacetyl rifampicin (DAc-RIF) and 14-hydroxyclarythromcin (14OH-CLR) in DBS samples. A clinical application study was performed in tuberculosis patients by comparing DBS concentrations with plasma concentrations. The interaction between RIF and the DBS matrix was avoided using the complexing agents EDTA and DFX, which improved recoveries and matrix effects. The developed sample procedure resulted in a simple and fast method for the simultaneous quantification of RIF, CLR and their metabolites in DBS samples. High stability was observed as all four substances were stable at ambient temperature for 2 months. Deming regression analysis of the clinical application study showed no significant differences for RIF, DAc-RIF, CLR and 14OH-CLR between patient plasma and DBS analysis. The slopes of the correlation lines between DBS and plasma concentrations of RIF, DAc-RIF, CLR and 14OH-CLR were 0.90, 0.99, 0.80 and 1.09 respectively. High correlations between plasma and DBS concentrations were observed for RIF (R(2)=0.9076), CLR (R(2)=0.9752) and 14OH-CLR (R(2)=0.9421). Lower correlation was found for DAc-RIF (R(2) of 0.6856). The validated method is applicable for TDM of RIF, CLR and their active metabolites. The stability of the DBS at high temperatures can facilitate the TDM and pharmacokinetic studies of RIF and CLR even in resource limited areas. The role of EDTA and DFX as complexing agents in the extraction was well investigated and may provide a solution for potential applications to other DBS analytical methods.

Simultaneous Determination of Rifampicin and Isoniazid in Urine and Pharmaceutical Formulations by Multivariate Visible Spectrophotometry

Partial least squares regression (PLSR) was used for the simultaneous quantification of rifampicin (RIF)and isoniazid (INH) by visible spectrophotometry using a simple derivatization reaction. In the presence of neocuproine, copper(II) is easily reduced by INH to a Cu(I)-neocuproine complex that shows an absorption maximum at 455 nm. Under these conditions, RIF shows an absorption maximum at 449 nm. The calibration set was established between 8and 57 mg L-1 for RIFand 1.5and 7 mg L-1 for INH. The method was applied to the determination of the drugs in urine samples (recoveries between 92and 119%)and in pharmaceutical formulations (relative error lower than 5%).

Simultaneous determination of rifampicin and levofloxacin concentrations in catheter segments from a mouse model of a device-related infection by liquid chromatography/electrospray ionization tandem mass spectrometry

The aim of this study was to develop a specific and sensitive liquid chromatography mass spectrometry (LC/MS) method for the determination of rifampicin and levofloxacin concentrations from infected tissues within teflon catheter segments which were subcutaneously implanted in mice. A solid-phase extraction procedure was used to extract analytes from tissue homogenates of the catheter segments and reverse-phase HPLC combined with positive electrospray ionization mass spectrometry was used for analyte separation and quantification. The assay was found to be linear over the concentration range of 0.02–2 μg/g for rifampicin and levofloxacin in tissues and provided good validation data for accuracy and precision. The intra-day accuracy as determined by the relative error was −1.3% for levofloxacin and 6.1% for rifampicin, and precision was evaluated by R.S.D.s with a maximum of 5.1% for levofloxacin and 8.1% for rifampicin. The inter-day accuracy was −3.3% for levofloxacin and −4.6% for rifampicin, and precision was 8.6% for levofloxacin and 7.1% for rifampicin. The assay uses less tissue than previously described methods and can be applied to determine the penetration of rifampicin and the fluoroquinolone in catheter segments from a mouse model of a device-related infection. Finally, the HPLC–MS assay should be applicable to studies of rifamycin + quinolone combination therapies in other animal models of bacterial infection.

Simultaneous determination of rifampicin and sulbactam in mouse plasma by high-performance liquid chromatography

A simple and rapid high-performance liquid chromatographic (HPLC) method with ultraviolet detection has been developed and validated for the simultaneous determination of rifampicin and sulbactam in mouse plasma. Plasma samples were deproteinized with acetonitrile and separated by HPLC on a RP-18 (125 x 4 mm, 5 microm) column and gradient elution with potassium dihydrogen phosphate solution (pH 4.5; 50 mm) and acetonitrile at a flow-rate of 1.0 mL/min. Rifampicin and sulbactam were monitored at 230 nm and confirmed by means of their UV spectra using a diode-array detector. The method was linear at plasma levels from 1 to 100 microg/mL for rifampicin and from 5 to 200 microg/mL for sulbactam. The limits of quantification were 0.6 microg/mL for rifampicin and 4.2 microg/mL for sulbactam. The intra- and inter-day precisions of the method (RSD) were lower than 5% for both compounds. Average recoveries of rifampicin and sulbactam from mice plasma were 98.2 and 89.3%, respectively. The developed method was successfully applied to the determination of the pharmacokinetic profile of both compounds in mice.

Simultaneous densitometric determination of rifampicin and isoniazid by high-performance thin-layer chromatography

High-performance thin-layer chromatography (HPTLC) on silica gel 60 F 254 TLC plates, with ethyl acetate-methanol-acetone-acetic acid, 5 + 2 + 2 + 1, as mobile phase, has been used for simultaneous determination of rifampicin and isoniazid. Quantitative analysis was accomplished by UV-visible densitometric scanning.

Simultaneous determination of rifampicin and efavirenz in plasma.

Complex drug interactions involving antiretroviral agents and drugs for the management of opportunistic infections demand the monitoring of plasma drug concentrations to prevent treatment failure. The high occurrence of tuberculosis in HIV-infected subjects makes the management of HIV treatment complex. Rifampicin, a potent inducer of the cytochrome P 450 metabolic pathway, is a very active antituberculosis drug that accelerates the metabolism of protease inhibitors. Regimens containing efavirenz, a non-nucleoside reverse transcription inhibitor, could be an alternative, but efavirenz plasma concentrations may be altered after the coadministration of rifampicin. Efavirenz is also a cytochrome P 450 inducer and may alter rifampicin plasma levels. Due to the increasing need to monitor plasma concentrations in HIV patients with tuberculosis, a high-performance liquid chromatographic (HPLC) method has been developed to measure rifampicin and efavirenz at the same time in a small amount of sample. This HPLC method is highly sensitive and precise, suitable for pharmacokinetic studies or routine clinical monitoring of rifampicin and efavirenz simultaneously in HIV patients with tuberculosis.

A Validated Reversed-Phase (C<SUB>18</SUB>) HPLC Method for Simultaneous Determination of Rifampicin, Isoniazid and Pyrazinamide in USP Dissolution Medium and Simulated Gastric Fluid

A liquid-chromatographic reversed-phase method employing a C18 column has been developed for simultaneous analysis of rifampicin, isoniazid and pyrazinamide in 0.1 M hydrochloric acid dissolution medium and in simulated gastric fluid. Good separations were achieved by employing a gradient prepared from methanol and 0.01M sodium dihydrogen orthophosphate buffer containing 0.05% w/v tetramethylammonium chloride (pH adjusted to 3.5). The detection wavelength was 254 nm. The method was validated for linearity, accuracy, precision and ruggedness. It was found to work well for analysis of the three drugs in the presence of degradation products and even for samples containing ethambutol, which does not interfere because of lack of UV absorption.

Simultaneous determination of rifampicin, isoniazid and pyrazinamide in tablet preparations by multivariate spectrophotometric calibration

The use of multivariate spectrophotometric calibration is presented for the simultaneous determination of the active components of tablets used in the treatment of pulmonary tuberculosis. The resolution of ternary mixtures of rifampicin, isoniazid and pyrazinamide has been accomplished by using partial least squares (PLS-1) regression analysis. Although the components show an important degree of spectral overlap, they have been simultaneously determined with high accuracy and precision, rapidly and with no need of nonaqueous solvents for dissolving the samples. No interference has been observed from the tablet excipients. A comparison is presented with the related multivariate method of classical least squares (CLS) analysis, which is shown to yield less reliable results due to the severe spectral overlap among the studied compounds. This is highlighted in the case of isoniazid, due to the small absorbances measured for this component.

Simultaneous determination of rifampicin, isoniazid and pyrazinamid by high performance thin layer chromatography

Simultaneous determination of rifampicin, isoniazid and pyrazinamid by high performance thin layer chromatography