Determination Of Carvedilol Research Articles

A unique revolutionary eco-friendly spectrophotometric technique for solving the spectral overlap in the determination of carvedilol and ivabradine in their binary combination: stability study

BackgroundCarivalan® dosage form containing carvedilol and ivabradine is widely indicated for patients with stable angina. Three precise, eco-friendly and reproducible spectrophotometric techniques were created for resolving the researched drugs in their mixtures using zero and/or ratio spectra. Technique I is a factorized dual wavelength coupled with spectrum subtraction (FDW-SS), technique II is a ratio difference, and technique III is a constant center coupled with spectrum subtraction (CC-SS). Moreover, CAR and IVA were simultaneously determined in the existence of their oxidative degradation products exploiting the newly developed induced tripartite amplitude difference coupled with ratio subtraction (ITAD-RS) technique.ResultsThe calibration curves for CAR and IVA showed linearity within 3.0–30.0 µg/ml, each. Techniques' precision, accuracy, and linearity ranges were resolved and validated in harmony with ICH guidelines. Additionally, the specificity was examined by examining created combinations of the proposed drugs with LOD of 0.258 and 0.290 for CAR, while for IVA 0.272 and 0.204.ConclusionThese techniques were used to determine the presence of the provided drugs in Carivalan® tablets. There is statistical comparison between the found results of the offered spectrophotometric techniques and the previously reported ones with no discernible variance in the acquired results.

Cardiovascular drugs and suicide death: Determination of carvedilol, amlodipine, doxazosin and diltiazem in two fatal cases

A number of medical conditions are identified as risk factors for suicide death; in particular, cardiovascular illnesses are recognized as a major suicide risk factor. In this case, self-poisoning is the common method of suicide and cardiovascular drugs are among the major medications associated with fatal overdose, with calcium channel blockers being one of the most common agents. The present study describes two different fatal suicide cases involving four cardiovascular drugs: carvedilol, doxazosin and amlodipine (case 1) and diltiazem (case 2). The concentrations of the target cardiovascular drugs in the different biological specimens (central and femoral blood, urine, liver, brain) are presented, giving information about the potentially fatal data and the distribution of the drugs in the body. The study led to the implementation of a fast, sensitive and simple method for the detection and quantification of the four commonly prescribed cardiovascular drugs in post-mortem specimens including fluids and tissues for forensic purposes. The method was fully validated. The toxicological results of the studied cases are discussed, along with the autopsy results, histopathological evidence, and circumstances of death. The toxicological findings presented in the study provide new data regarding cardiovascular drugs in different post-mortem specimens, which will contribute to the currently limited knowledge about the toxicological profile of cardiovascular drugs and their distribution.

A flexible and sensitive electrochemical sensing platform based on dimethyl sulfoxide modified carbon cloth: towards the detection of dopamine and carvedilol.

The determination of neurotransmitters and adrenoreceptor drugs is highly essential due to their specific functions in the human body. In this work, the determination of carvedilol (CAR) and dopamine (DA) was carried out using carbon cloth (CC), which was modified using a facile strategy of drop-casting dimethyl sulfoxide (DMSO). This induced the formation of functional groups without any loss in the structural integrity of CC. The DMSO modified CC (CC-DMSO) was used for the detection of CAR in the range of 1 nM to 10 μM with a limit of detection (LOD) of 120 pM. Similarly, the CC-DMSO was able to detect DA in the range of 10 pM to 10 μM with a highly promising LOD of 0.3 pM. A bending test was also carried out on the electrode and it could be seen that only a negligible variation in sensing capability was observed when the electrode was in the bent form. In addition, the detection of CAR and DA was also carried out in real samples such as human serum. This study reveals that this modification strategy can serve as a versatile and flexible sensing platform for the detection of CAR and DA together in real world medical scenarios.

Spectrophotometric Determination of Carvedilol via Oxidation and Bleaching Color of Methyl Red

Spectrophotometric Determination of Carvedilol via Oxidation and Bleaching Color of Methyl Red

Development of a simple, rapid, accurate, and sensitive method for carvedilol analysis in human blood serum by reversed phase-high performance liquid chromatography with diode array detector

Carvedilol is a drug used in the treatment of serious cardiovascular diseases. Therefore, the development of a new method for analyzing the therapeutic and toxic concentrations of carvedilol in human blood serum is very important. In this study, a simple, rapid, accurate, and sensitive method was developed using isocratic reversed phase-high performance liquid chromatography with diode array detector for the determination of carvedilol (a nonselective beta-blocker) in human blood serum. The separation was achieved with a Supelco Discovery C18 reversed phase column, using acetonitrile and 1% (v/v) of triethylamine aqueous solution (pH 3.5) as mobile phase. The method was optimized and subsequently validated. Method validation was performed by evaluating precision, accuracy, selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), stability, robustness, and system suitability parameters. Relative standard deviation (%) values for the repeatability study were very low. The calibration curve was found to be linear over the concentration range of 100–1000 μg/L (R2 = 0.9999). The average recovery was obtained as 99.83 ± 0.84%. The LOD and the LOQ for carvedilol was determined to be 56.63 and 171.61 ng/L, respectively. The results obtained from this study demonstrated that the validated method can be successfully used to analyze the therapeutic and toxic concentrations of carvedilol in human blood serum. Furthermore, this new method is applicable for large sample series in laboratory studies.

HPLC Determination of Carvedilol, Candesartan Cilexetil and Hydrochlorothiazide in Their Bulk and Tablet Dosage Forms

An isocratic HPLC method was developed for rapid simultaneous separation and determination of carvedilol, candesartan cilexetil and hydrochlorothiazide in pure and tablet dosage form. Separation was carried out on a Hypersil gold C18 (15 μm, 100 x 4.6 mm) column. Mobile phase composed of methanol, acetonitrile and 0.1% ortho-phosphoric acid in the ratio of (35:50:15, v/v/v). The flow rate was 0.8 ml/min and UV detection was measured at 215 nm. Linearity range was observed from 1–90 μg/ml for the three drugs. The proposed method was validated in terms of linearity, accuracy, precision and limits of detection and quantitation according to ICH. The obtained results were compared with reference methods.

СПЕКТРОФОТОМЕТРИЧНЕ ВИЗНАЧЕННЯ КАРВЕДІЛОЛУ В ТАБЛЕТКАХ

<p><strong>SPECTROPHOTOMETRIC DETERMINATION OF CARVEDILOL IN TABLETS</strong></p><p><strong>Y. Zhuk, S. Vasjuk, I. Ver</strong><strong>оvkina</strong></p><p>Zaporozhye State Medical University, Zaporozhye</p><p><strong>Summary:</strong> in this investigation a visible spectrophotometric method for the determination of carvedilol based on the absorbance of colored product of the reaction between carvedilol and bromcresol purple in acetone medium at 399 nm measurement was developed. The optimal conditions for the quantitative determination of carvedilol in the content of pharmaceutical drugs were established. The validation of the worked out procedure on such validated characteristics as linearity, precision, accuracy and robustness was carried out.</p><p><strong>Keywords:</strong> spectrophotometric analysis, carvedilol, bromcresol purple.</p><p><strong>Introduction. </strong>Carvedilol (1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-2) belongs to a group of medicines called beta-adrenergic blocking agents, that are indicated for the treatment of hypertension angina pectoris and heart failure.</p><p>Our aim is to develop a simple, accurate and valid method for the spectrophotometric determination of carvedilol.</p><p>Purposes:</p><ul><li>establish optimal conditions of the photometric reaction between carvedilol and bromcresol purple;</li><li>develop the method for the determination of carvedilol in pharmaceutical formulations;</li><li>carry out validation of the worked out procedure.</li></ul><p><strong>Methods of analysis.</strong></p><p>Object of research: tablets «Corvazan» 25 mg (Arterium), tablets «Coriol» 12,5 mg (KRKA), tablets «Coriol» 25 mg (KRKA).</p><p>Reagents and Chemicals: standard solution of carvedilol, bromcresol purple, acetone. All reagents and chemicals used were of analytical grade.</p><p>Instrument: spectrophotometer Specord 200, electronic balance ABT-120-5PM, ultrasonic bath ELMASONIC 60Н.</p><p><strong>Results and discussion</strong>.</p><p>Linearity. The analytical parameters such as molar absorptivity, Beer’s law limits and Sandell’s sensitivity values were calculated.</p><p>Precision. The developed methods give the result with repeatability sufficient for dependable determination the investigated substance in pharmaceutical formulations.</p><p>Accuracy. Accuracy established by analyte addition technique.</p><p>Robustness. Determined factors that influence on the absorbance value: reagent quantity and timing stability.</p><p>Sample solutions stable during 30 min.</p><p>Addition to sample solution ±10 % bromcresol purple solution is not change the absorbance value.</p><p><strong>Conclusions. </strong>Established that reaction between carvedilol and bromcresol purple proceeds in acetone medium at room temperature.</p><p>Molar absorption coefficient is 2,13·10<sup>4</sup>.<strong></strong></p><p>Developed the method of spectrophotometric determination of carvedilol in pharmaceutical formulations.</p><p>Proved that the method is valid on such validated characteristics as linearity, precision, accuracy and robustness. </p>

Magnetic Retrieval of Ionic Liquids: High Sensitivity Fluorescence Determination of Carvedilol in Tablets, Plasma, and Urine

ABSTRACTIonic liquid-based dispersive liquid–liquid microextraction with magnetic dispersive micro-solid phase extraction was employed to determine carvedilol, an anti-arrhythmic drug, with fluorescence detection. The ionic liquid extractant was magnetically retrieved with unmodified nanoparticles. The 1-Octyl-3-methylimidazolium hexafluorophosphate was used to extract the analyte. Magnetite nanoparticles were added to adsorb the ionic liquid. The loaded magnetite nanoparticles were collected by a magnetic field. The ionic liquid and carvedilol were recovered from the surface of the magnetite nanoparticles by sonication in the presence of ethanol. The analyte was determined by fluorescence with excitation at 244 nm and emission at 355 nm. Under the optimized conditions, the calibration graph was linear from 0.4 ng mL−1 to 80 ng mL−1 with a detection limit of 0.1 n g mL−1. The relative standard deviation for carvedilol was 1.57%. The method was used to determine the analyte in tablets, human plasma, and urine with recoveries between 95.04 and 106.6%.

A new HPLC Method for Determination of Carvedilol in Human Plasma and its Application in Bioequivalence Studies

A new HPLC Method for Determination of Carvedilol in Human Plasma and its Application in Bioequivalence Studies

Simultaneous Determination of Carvedilol and Hydrochlorothiazide in Pharmaceutical Dosage Form by Second Order Derivative UV Spectrophotometry

Derivative spectrophotometry offers a useful approach for the analysis of drugs in multi-component formulation. In this study a second order derivative spectrophotometric method is applied for the simultaneous determination of Carvedilol and Hydrochlorothiazide in tablet dosage form. The measurements were carried out at wavelengths of 292 and 272 nm for Carvedilol and Hydrochlorothiazide respectively. The method was found to be linear (r2=0.999) in the range of 5–25 μg/ml for Carvedilol in the presence of 20 μg/ml of Hydrochlorothiazide at 292 nm. The linear correlation (r2=0.999) was obtained in the range of 5–25 μg/ml for Hydrochlorothiazide in the presence of 20 μg/ml of Carvedilol at 272 nm. The method was successfully used for simultaneous determination of Carvedilol and Hydrochlorothiazide in tablet dosage form without any interference from excipients and prior separation.

Validated Sensitive Spectrophotometric methods for Determination of Carvedilol and Nebivolol HCl in dosage forms.

A simple, sensitive and rapid spectrophotometric methods were developed and validated for the determination of two antihypertensive drugs namely, carvedilol and nebivolol hydrochloride in pure form and pharmaceutical formulations. Method (I) is based on the formation of a binary complex between the studied drugs and eosin Y in presence of tween 80 at (pH 3.0).The formed complex exhibited maximum absorption at 545 nm for carvedilol and 543 nm for nebivolol. The concentration plots were rectilinear over concentration range of 0.5-5 and 1-7 µg/mL with lower detection limits of 0.09 and 0.11µg/mL and lower quantitation limits of 0.28 and 0 .34 µg/mL for carvedilol and nebivolol respectively. Method (II) is based on the reaction of studied drugs through their secondary amino groups with 2, 4-dinitrofluorobenzene (DNFB) at pH 8 to form yellow colored reaction products peaking at 383 nm and 390 nm for carvedilol and nebivolol, respectively. The absorbance-concentration plots were rectilinear over the concentration ranges of 5-30 and 4-28 µg/ mLwith the lower detection limits of 0.48 and 0.51 µg/mL and the lower quantitation limits of 1.45 and 1.54 µg/mL for cavredilol and nebivolol respectively. The different experimental parameters affecting the development and stability of the formed complex and reaction products were carefully studied and optimized for both methods. Both methods were successfully applied for determination of the studied drugs in their dosage forms.

Development of a highly sensitive and selective spectrophotometric method for the determination of carvedilol in pharmaceutical and urine samples

A simple, sensitive, selective, accurate and cost-effective spectrophotometric method for the determination of CAR in pharmaceutical and urine samples was developed.

Simultaneous chiral separation and determination of carvedilol and 5′-hydroxyphenyl carvedilol enantiomers from human urine by high performance liquid chromatography coupled with fluorescent detection

Abstract A sensitive and specific high performance liquid chromatography coupled with fluorescent detection (HPLC-FL) and tandem mass spectrometry detection (HPLC-MS/MS) methods for separation and determination of carvedilol (CAR) enantiomers and 5′-hydroxyphenyl carvedilol (5′-HCAR) enantiomers has been developed and validated. The analysed compounds were extracted from human urine by solid phase extraction. Good enantioseparation of the studied enantiomers was achieved on CHIRALCEL® OD-RH column using 0.05% trifluoroacetic acid and 0.05% diethylamine in water and acetonitrile in a gradient elution. The mass spectrometric data were acquired using the multiple reaction monitoring mode by positive electrospray ionisation. The method was validated over the concentration range from 25.0 ng mL−1 to 200 ng mL−1 for the analysed compounds. The limit of quantification varied from 14.2 ng mL−1 to 24.2 ng mL−1. Both the repeatability and inter-day precisions were below 10.0%, and the accuracy varied from −13.2% to 3.77%. The extraction recoveries ranged from 79.2% to 108%. The present paper reports the method for the simultaneous determination of CAR enantiomers and their metabolite enantiomers (5′-HCAR) in human urine samples. This newly developed method was successfully used to analyse the aforementioned analytes in human urine samples obtained from patients suffering from cardiovascular disease.

Validated Stability-Indicating Capillary Electrophoresis Method for the Separation and Determination of a Fixed-Dose Combination of Carvedilol and Hydrochlorothiazide in Tablets

A novel, fast, sensitive, and specific capillary electrophoresis (CE) technique coupled to a diode array detector has been developed for the separation and simultaneous determination of carvedilol (CRV) and hydrochlorothiazide (HCT) in two combination formulations. The proposed method utilized a fused silica capillary (55 cm x75 microm id) and the background electrolyte solution phosphate buffer (12.5 mM, pH 7.4)-methanol (95+5, v/v). The separation was achieved at 30 kV applied voltage and 24 degree C. Atorvastatin (80 microg/mL) was chosen as the internal standard. The described method was linear over the range of 1-200 and 0.2-150 microg/mL for CRV and HCT, respectively. Intraday and interday RSD (n = 6) was < or =1.4%. The LOD values of CRV and HCT were 0.26 and 0.07 microg/mL, respectively. The validated CE method was successfully applied to the analysis of two commercial tablet dosage forms. Forced degradation studies were performed on bulk samples of the two drugs using thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation products produced as a result of stress studies did not interfere with the determination of CRV and HCT; the assay could, therefore, be considered stability-indicating.

Simultaneous Determination of Carvedilol and Hydrochlorothiazide in Tablets and Spiked Human Plasma using Derivative Spectrophotometry

Quick and accurate methods for determination of carvedilol and hydrochlorothiazide in tablets and spiked human plasma by using third derivative (3D), fourth derivative (4D) and ratio spectra derivative (1DD) spectrophotometric methods were developed. The zero-crossing technique was employed in measurements, using 3D at 245.9 or 230.2 nm and 4D at 247.4 or 226.9 nm for carvedilol or hydrochlorothiazide, respectively. The first-derivative of ratio spectra (1DD) where the amplitudes were measured at 236.1 nm for carvedilol and 261.1 nm for hydrochlorothiazide. The calibration curves were linear in the ranges of 1.0-20.0 μg mL-1 for each of carvedilol and hydrochlorothiazide using 3D 4D and 1DD methods. The suggested methods were tested using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations. The methods retained their accuracy and precision when the standard addition technique was applied. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by reported and official HPLC methods for carvedilol and hydrochlorothiazide, respectively. These methods showed to be appropriate for simultaneous determination of carvedilol and hydrochlorothiazide in human plasma samples with a limit of quantitation (LOQ) is ≤ 0.5 μg mL-1.

Determination of Carvedilol in Human Plasma by Gas Chromatography-Mass Spectrometry Method

An analytical procedure was developed and validated for the quantitation of carvedilol in human plasma. Carvedilol and atenolol (internal standard) were extracted from human plasma with a mixture of diethylether and ethylacetate at basic pH with liquid‐liquid extraction. The extracts were derivatized with nMethyl-n-(trimethylsilyl)trifluoroacetamide and analyzed by gas chromatography-mass spectrometry (GC‐MS). Calibration curves were linear over the concentration range 15‐500 ng/mL. Intra- and inter-day precision, expressed as the relative standard deviation were less than 8.0%, and accuracy (relative error) was better than 11.0%. The limits of detection and quantification of carvedilol were 5.0 and 15 ng/mL, respectively. Also, the method was successfully applied to three patients with hypertension who had been given an oral tablet of 25 mg carvedilol.

Application of a Sensitive, Rapid and Validated LC–MS–MS Method for the Determination of Carvedilol in Human Plasma

Carvedilol was quantified in human plasma after a single 25 mg oral dose of the drug was given to 26 healthy volunteers. An applied Biosystems Sciex API 3200 triple quadrupole mass spectrometer in multiple reaction monitoring mode, using electrospray ionization in the positive ion mode was used. Simple solid phase extraction was followed by C18 reverse phase chromatography and tandem mass spectrometric detection using propranalol as the internal standard. The mean recovery for carvedilol was 91.2% with a lower limit of quantification of 0.5 ng mL−1. This validated assay method makes use of the increased sensitivity and selectivity of tandem mass spectrometry detection to allow for a more rapid and selective method for the determination of carvedilol in human plasma.

New RP‐HPLC Method with UV‐Detection for the Determination of Carvedilol in Human Serum

Carvedilol has been used as an antihypertensive drug and also possesses antioxidant and antiproliferative effects. A simple and sensitive analytical method for carvedilol in human serum by using high performance liquid chromatography (HPLC) was developed. The method employs a liquid‐liquid extraction for isolation and sample concentration followed by reversed phase liquid chromatography (RPLC) analysis using ultraviolet (UV) detection at 238 nm. Analytes were extracted from serum samples, that were previously mixed with 300 µL of 0.1 N sodium hydroxide solution into an n‐hexane, dichloromethane (7∶3) solvent system. The mobile phase was made of acetonitrile, 15 mM orthophosphoric acid (37∶63), and 0.25% v/v of triethylamine, with a flow rate of 1 mL/min. Serum samples containing the carvedilol and internal standard, amitriptyline were eluted through a C8, Kromasil KR 100 5C8 column. Retention times of carvedilol and amitriptyline were 6.10 min and 8.44 min, respectively. The intra day and inter day coefficient of variation and percent error values of the assay method were less than 5%. The calibration curve was linear over a concentration range of 5–500 ng/mL. The extraction recovery of carvedilol is more than 75%. The validated method was applied to a pharmacokinetic study of carvedilol in human serum following the administration of a single carvedilol tablet (6.25 mg). Such a method would be ideally suitable for estimation of the drug for pharmacokinetic studies in human volunteers after oral administration of a single or multiple dosage(s) of carvedilol.

Extractive spectrophotometric method for determination of carvedilol in tablets

A sensitive and rapid extractive spectrophotometer method has been developed for the assay of carvedilol in pharmaceutical formulations. The method is based on the formation of a chloroform soluble ion-pair complex between carvedilol and bromocresol green in an acidic medium. The complex shows absorption maximum at 415 nm and the system obeys Beer's law in the concentration range of 5-25 µg/ml. The results obtained by the proposed method were validated statistically and by recovery studies.

Validation of UV Spectrophotometric and Nonaqueous Titration Methods for the Determination of Carvedilol in Pharmaceutical Formulations

Ultraviolet (UV) spectrophotometric and nonaqueous volumetric methods are described for the determination of carvedilol in pharmaceutical formulations. Linearity, precision, and accuracy were evaluated according to the validation guidelines of the International Conference on Harmonization and the United States Pharmacopeia for both methods. The UV spectrophotometric procedure was performed in ethanol at 244 nm. Good linearity was obtained between 2 and 7 microg/mL with a correlation coefficient of 0.9999. The intra- and interday precision values were <2% for all samples analyzed. The accuracy, determined from recovery studies, was between 97.5 and 102.2%. The other procedure was based on the volumetric quantitation of carvedilol in a nonaqueous medium with 0.01 M perchloric acid and 1% violet crystal as the indicator. The validation of the volumetric method yielded good results that included linearity (r of > 0.999), precision (relative standard deviations of <2% for intra- and interday precision), and accuracy (96.4-102.4%). The methods were applied to tablets and compounded capsules. Statistical analysis by analysis of variance showed no significant difference between the results obtained by the proposed methods.